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1.  A cluster randomized trial of utilizing a local change team approach to improve the delivery of HIV services in correctional settings: study protocol 
Health & justice  2013;1(1):8-.
Background
Persons held in correctional facilities are at high risk for HIV infection and their prevalence of HIV is substantially higher than in the general population. Thus, the need for proper surveillance and care of this high risk population is a paramount public health issue. This study aims to evaluate an organization-level intervention strategy for improving HIV services for persons in prison or jail.
Methods/Design
HIV Services and Treatment Implementation in Corrections (HIV-STIC) is using a cluster randomized trial design to test an organization-level intervention designed to implement improvements in preventing, detecting, and treating HIV for persons under correctional supervision. Matched pairs of prison or jail facilities were randomized using a SAS algorithm. Facility staff members in both Experimental and Control conditions involved in HIV service delivery are recruited to receive training on HIV infection, the HIV services continuum, and relevant web-based resources. Staff members in both conditions are tasked to implement improvements in HIV prevention, testing, or treatment in their facility. In the Control condition facilities, staff participants use existing techniques for implementing improvement in a selected area of HIV services. In contrast, the Experimental condition staff participants work as a Local Change Team (LCT) with external coaching and use a structured process improvement approach to improve a selected part of the HIV services continuum. The intervention period is 10 months during which data are obtained using survey instruments administered to staff members and aggregate services delivery data. The study is being implemented in 13 pairs of correctional facilities across nine states in the US. Experimental sites are hypothesized to show improvements in both staff attitudes toward HIV services and the number and quality of HIV services provided for inmates.
Discussion
The current study examines a range of process and outcome data relevant to the implementation of a Change Team approach across diverse correctional settings in the United States. This initial study represents an important step toward a national best practices approach to implementing change in U.S. correctional settings and could serve as an exemplar for designing similar implementation studies.
doi:10.1186/2194-7899-1-8
PMCID: PMC4270366  PMID: 25530933
HIV; Correctional facility; NIATx; Change team
2.  Predictors of non-diagnostic cytology in surgeon-performed ultrasound guided fine needle aspiration of thyroid nodules 
Background
Fine needle aspiration (FNA) is the standard of care for the diagnostic work-up of thyroid nodules but despite its proven utility, the non-diagnostic rate for thyroid FNA ranges from 6-36%. A non-diagnostic FNA is problematic for the clinician and patient because it can result in repeated procedures, multiple physician visits, and a delay in definitive treatment. Surgeon-performed FNA has been shown to be safe, cost-effective, as accurate as those performed by other clinicians, and has the added benefit of decreasing wait times to surgery. Several studies have examined rates and factors that may be predictive of a non-diagnostic cytology in non-surgeon FNA, but none have evaluated this in surgeon-performed thyroid FNA. If these factors are unique in surgeon-performed vs. non-surgeon performed thyroid FNA, then patients may be more appropriately triaged to FNA by alternate clinicians.
Objectives
The purpose of this study was to determine the rate and factors predictive of a non-diagnostic FNA in surgeon performed ultrasound-guided FNA of thyroid nodules.
Methods
We conducted a retrospective review of all adult patients who underwent thyroid FNA by a staff, fellow, or resident Otolaryngologist at the University of Alberta between January 2011 and June 2013. Factors analyzed included patient factors, thyroid characteristics, nodule characteristics, and surgeon level of training and experience. Univariate and multivariate binary logistic regression analysis were performed.
Results
131 patients (180 nodules) were reviewed. The non-diagnostic rate was 23%. Nodules with predominant cystic component, those less than 1 cm, and resident-performed FNA were associated with non-diagnostic cytology (p = 0.001, p = 0.02, p = 0.04 respectively). A cystic nodule was the only independent predictor of non-diagnostic FNA on multivariate analysis (OR = 4.441, 95% CI [1.785-11.045], p = 0.001).
Conclusions
The rate of non-diagnostic thyroid FNA performed by a surgeon with ultrasound guidance is similar to other clinicians. A cystic nodule is a strong independent predictor of non-diagnostic cytology. Non-cystic nodules may particularly benefit from surgeon-performed thyroid FNA due to the high diagnostic rate and potential for earlier definitive management.
doi:10.1186/s40463-014-0048-0
PMCID: PMC4260212  PMID: 25466726
Thyroid nodule; FNA; Diagnostic yield; Ultrasound
3.  Metabolic tumour volume as a prognostic factor for oral cavity squamous cell carcinoma treated with primary surgery 
Background
Metabolic tumour volume (MTV) obtained from pre-treatment 18 F-fluorodeoxydeglucose positron emission tomography with computed tomography (PET-CT) has been validated as an independent predictive factor of outcomes in head and neck cancer patients (HNC) treated with primary chemoradiotherapy (CRT). However its role in patients treated with primary surgery has not yet been studied.
Objective
To evaluate the prognostic value of MTV in patients treated with primary surgery for oral cavity squamous cell carcinoma (OCSCC).
Method
Demographic and survival data was obtained from patients diagnosed with OCSCC from 2008–2012 in Alberta, Canada. All patients included in the study had PET-CT scan before curative surgical resection. MTV and maximum standardized uptake value (SUVmax) value was delineated from pre-treatment PET-CT scans using Segami Oasis software (Columbus, OH). MTV and SUVmax were divided into intertertile thirds before statistical analysis to allow for in-group comparison of survival.
Results
A total of 80 patients were analyzed using SPSS ver. 20.0 (SPSS Inc, Chicago, IL). Five-year overall, and disease-free survival using Kaplan-Meier curves were 70% and 73% respectively. When the combined SUVmax (tumour primary and locoregional metastasis) was evaluated, it failed to predict overall (HR = 1.0, p = 0.99) or disease-free survival (HR = 1.0, p = 0.227).
Conversely an increase in MTV of 17.5 mL (difference between the highest and lowest MTV tertile) was associated with a 12.4 fold increase in risk of disease recurrence (p < 0.001) and an 11.2 fold increase in the risk of death (p < 0.05).
Conclusions
This study shows that MTV is an independent adverse prognostic factor for death and disease recurrence in OCSCC treated with primary surgery.
doi:10.1186/s40463-014-0033-7
PMCID: PMC4198685  PMID: 25312990
Metabolic tumour volume; Standardized uptake value; Imaging; Tumour marker; Head and neck cancer
4.  Quantifying cell-generated mechanical forces within living embryonic tissues 
Nature methods  2013;11(2):183-189.
Cell-generated mechanical forces play a critical role during tissue morphogenesis and organ formation in the embryo. However, little is known about how these forces shape embryonic organs, mainly because it has not been possible to measure cellular forces within developing three-dimensional (3D) tissues in vivo. Here we present a method to quantify cell-generated mechanical stresses that are exerted locally within living embryonic tissues using fluorescent, cell-sized, oil microdroplets with defined mechanical properties and coated with surface integrin or cadherin receptor ligands. After introducing a droplet between cells in a tissue, local stresses are determined from the droplet shape deformations, which are obtained via fluorescence microscopy and computerized image analysis. Using this method, we quantify the anisotropic stresses generated by mammary epithelial cells cultured within 3D aggregates and confirm that these stresses (3.4 nN/µm2) are dependent on myosin II activity and more than two-fold larger than the stresses generated by cells of embryonic tooth mesenchyme when analyzed within similar cultured aggregates or in developing whole mouse mandibles.
doi:10.1038/nmeth.2761
PMCID: PMC3939080  PMID: 24317254
5.  Network-based inference from complex proteomic mixtures using SNIPE 
Bioinformatics  2012;28(23):3115-3122.
Motivation: Proteomics presents the opportunity to provide novel insights about the global biochemical state of a tissue. However, a significant problem with current methods is that shotgun proteomics has limited success at detecting many low abundance proteins, such as transcription factors from complex mixtures of cells and tissues. The ability to assay for these proteins in the context of the entire proteome would be useful in many areas of experimental biology.
Results: We used network-based inference in an approach named SNIPE (Software for Network Inference of Proteomics Experiments) that selectively highlights proteins that are more likely to be active but are otherwise undetectable in a shotgun proteomic sample. SNIPE integrates spectral counts from paired case–control samples over a network neighbourhood and assesses the statistical likelihood of enrichment by a permutation test. As an initial application, SNIPE was able to select several proteins required for early murine tooth development. Multiple lines of additional experimental evidence confirm that SNIPE can uncover previously unreported transcription factors in this system. We conclude that SNIPE can enhance the utility of shotgun proteomics data to facilitate the study of poorly detected proteins in complex mixtures.
Availability and Implementation: An implementation for the R statistical computing environment named snipeR has been made freely available at http://genetics.bwh.harvard.edu/snipe/.
Contact: ssunyaev@rics.bwh.harvard.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
doi:10.1093/bioinformatics/bts594
PMCID: PMC3509492  PMID: 23060611
6.  Policies and Practices in the Delivery of HIV Services in Correctional Agencies and Facilities: Results from a Multi-Site Survey 
HIV risk is disproportionately high among incarcerated individuals. Corrections agencies have been slow to implement evidence-based guidelines and interventions for HIV prevention, testing, and treatment. The emerging field of implementation science focuses on organizational interventions to facilitate adoption and implementation of evidence-based practices. A survey of among CJ-DATS correctional agency partners revealed that HIV policies and practices in prevention, detection and medical care varied widely, with some corrections agencies and facilities closely matching national guidelines and/or implementing evidence-based interventions. Others, principally attributed to limited resources, had numerous gaps in delivery of best HIV service practices. A brief overview is provided of a new CJ-DATS cooperative research protocol, informed by the survey findings, to test an organization-level intervention to reduce HIV service delivery gaps in corrections.
doi:10.1177/1078345813499313
PMCID: PMC3801270  PMID: 24078624
Corrections; Implementation; Staff survey; HIV policies; inmates
7.  Parole Officer–parolee Relationships and HIV Risk Behaviors during Community Supervision 
AIDS and behavior  2013;17(8):2667-2675.
We tested if good parole officer (PO)–parolee relationships reduce HIV risk behaviors during parole, as they do for risk of rearrest. Analyses used data from 374 parolees enrolled in a randomized clinical trial. Past month HIV risk behaviors were assessed by interview at baseline, 3- and 9-months after parole initiation. The Working Alliance Inventory and the Dual-Role Relationships Inventory measured PO relationship. Gender-stratified multivariate regressions tested associations of PO–parolee relationship with sex with multiple partners, unprotected sex with risky partner(s), and drug injection. Women parolees (n = 65) who reported better PO relationship characteristics were less likely to report having multiple sex partners [adjusted odds ratio: 0.82 (0.69, 0.98) at 3-months, 0.89 (0.80, 0.99) at 9-months], and, among those reporting multiple sex partners, had fewer partners on average [adjusted relative risk 0.98 (0.96, 0.99)]. These effects were not found among men. PO–parolee relationship quality can influence sexual risk behaviors among women parolees.
doi:10.1007/s10461-011-0081-1
PMCID: PMC3758401  PMID: 22038082
Parole; Community supervision; Working alliance; HIV risk behaviors; Women
8.  COLLABORATIVE BEHAVIORAL MANAGEMENT AMONG PAROLEES: DRUG USE, CRIME & RE-ARREST IN THE STEP’N OUT RANDOMIZED TRIAL 
Addiction (Abingdon, England)  2012;107(6):1099-1108.
Aims
To determine whether collaborative behavioral management (CBM) reduces substance use, crime and re-arrest among drug-involved parolees.
Design
Step’n Out was a randomized behavioral trial of CBM versus standard parole (SP) during 2004-2008. CBM adapted evidence-based role induction, behavioral contracting, and contingent reinforcement to provide parole officer/treatment counselor dyads with positive tools in addition to sanctions to manage parolees’ behavior over 12 weeks.
Setting
Six parole offices in five states in the U.S.A.
Participants
Parolee volunteers with a mandate for addiction treatment and a minimum of three months of parole (N=476). Follow-up was 94% at 3- and 86% at 9-months.
Measurements
Drug use and crime in a given month from calendar interviews 3- and 9-months after parole initiation, and re-arrests from criminal justice administrative data.
Findings
The CBM group had fewer months in which they used their primary drug (adjusted risk ratio (ARR) 0.20, 95% CI: 0.05, 0.78, p = .02) and alcohol (ARR 0.38, 95% CI: 0.22, 0.66, p=.006) over follow-up. CBM had its greatest effects among parolees who reported marijuana or another “non-hard” drug as their primary drug; parolees who preferred stimulants or opiates did not benefit. No differences were seen in total crime, re-arrests or parole revocations.
Conclusions
Collaborative behavioral management may reduce substance use among primary marijuana or other “non-hard” drug-using parolees without increasing revocations. Since the majority of drug violation arrests in the U.S. are for marijuana, these findings have important implications for the management of a substantial proportion of the U.S. community correctional population.
doi:10.1111/j.1360-0443.2011.03769.x
PMCID: PMC3321077  PMID: 22175445
9.  Limiting options: Sex ratios, incarceration rates and sexual risk behavior among people on probation and parole 
Sexually transmitted diseases  2012;39(6):424-430.
Background
To investigate how incarceration may affect risk of acquiring HIV and other sexually transmitted infections, we tested associations of ex-offenders’ sexual risk behavior with the male-female sex ratio and the male incarceration rate.
Methods
Longitudinal data from 1287 drug-involved persons on probation and parole as part of the Criminal Justice Drug Abuse Treatment Studies were matched by county of residence with population factors, and stratified by race/ethnicity and gender. Generalized estimating equations assessed associations of having unprotected sex with a partner who had HIV risk factors, and having more than 1 sex partner in the past month.
Results
Among non-Hispanic Black men and women, low sex ratios were associated with greater risk of having unprotected sex with a risky partner (Adjusted relative risk (ARR) = 1.76, 95% confidence interval (CI) = 1.29, 2.42; ARR = 2.48, 95% CI = 1.31, 4.73, respectively). Among non-Hispanic Black and non-Hispanic White women, low sex ratios were associated with having more than 1 sex partner (ARR = 2.00, 95% CI = 1.02, 3.94; ARR = 1.71, 95% CI = 1.06, 2.75, respectively). High incarceration rates were associated with greater risk of having a risky partner for all men (non-Hispanic Black: ARR= 2.14, 95% CI=1.39, 3.30; non-Hispanic White: ARR= 1.39, 95% CI: 1.05, 1.85; Hispanic: ARR = 3.99, 95% CI =1.55, 10.26) and having more than one partner among non-Hispanic White men (ARR= 1.92, 95% CI = 1.40, 2.64).
Conclusions
Low sex ratios and high incarceration rates may influence the number and risk characteristics of sex partners of ex-offenders. HIV-prevention policies and programs for ex-offenders could be improved by addressing structural barriers to safer sexual behavior.
doi:10.1097/OLQ.0b013e318254c81a
PMCID: PMC3575024  PMID: 22592827
criminal justice; racial/ethnic health disparities; sex ratios; parole/probation; social determinants; HIV/AIDS
10.  Primary surgery versus chemoradiotherapy for advanced oropharyngeal cancers: a longitudinal population study 
Background
Treatment for advanced stage oropharyngeal squamous cell carcinoma (OPSCC) includes combined chemoradiation therapy or surgery followed by radiation therapy alone or in combination with chemotherapy. The goal of this study was to utilize available evidence to examine survival outcome differences in patients with advanced stage OPSCC treated with these different modalities.
Methods
Patients with advanced stage OPSCC were identified. Primary outcome measurements were disease specific and overall survival rates with differences examined via Kaplan-Meier and logistic regression analysis.
Results
344 patients were enrolled. 94 patients underwent triple modality therapy inclusive of surgery followed by adjuvant combined chemotherapy and radiation therapy (S-CRT). 131 had surgery and radiation therapy (S-RT), while 56 had chemoradiation (CRT) therapy as their primary treatment. A total of 63 patients had single modality radiation therapy and were excluded from analysis due to the large number of palliative patients.
Kaplan-Meier overall survival analysis showed that therapy with S-CRT had the highest disease specific survival at five years (71.1%). This is contrasted against S-RT and CRT, with five year survival rates at 53.9%, and 48.6%, respectively.
Cox regression showed that the comparison of S-CRT vs. S-RT, and CRT is associated with statistically significant increased hazard ratios of 1.974, and 2.785, indicating that both S-RT and CRT are associated with a reduced likelihood of survival at 5 years when compared to S-CRT.
Conclusions
In this population based cohort study S-CRT is associated with a 17–22% 5 year disease specific survival benefit compared to CRT or S-RT.
doi:10.1186/1916-0216-42-31
PMCID: PMC3668157  PMID: 23663568
11.  Survival outcomes of patients with advanced oral cavity squamous cell carcinoma treated with multimodal therapy: a multi-institutional analysis 
Background
The oral cavity is the most common site for head and neck squamous cell carcinoma. Treatment of advanced stage oral cavity squamous cell carcinoma (OCSCC) has classically involved surgical resection with postoperative adjuvant radiotherapy (S-RT).Despite this aggressive dual modality therapy, the disease outcomes have remained poor. The treatment options expanded in 2004 when two international trials showed the addition of postoperative chemotherapy to radiation improved outcomes. These trials were, however not oral cavity site specific.
Objective
To assess survival outcomes of advanced OCSCC treated by differing modalities. The primary goal was to determine if the addition of postoperative chemotherapy (S-CRT) improves survival compared to other treatment regimens.
Methods
Demographic, pathologic, treatment, and survival data was obtained from patients diagnosed with OCSCC from 1998–2010 in Alberta, Canada. 222 patients were included in the final analysis from 895 OCSCC patients. Actuarial overall, disease-specific, disease-free, and metastasis-free survivals were estimated with Kaplan-Meier and Cox regression analyses. Patients were grouped by treatment.
Results
Patients receiving S-CRT had improved overall, disease-specific, disease-free, and metastasis-free survival compared to S-RT, CRT or RT(p < 0.05). Two and five year estimated overall survival was significantly higher in the S-CRT group at 77 and 58% (p < 0.05), versus S-RT with 55 and 40% rates(p < 0.05). Results were similar for disease-specific, disease-free, and metastasis free survival with S-CRT being favoured. Patients with extracapsular spread (ECS) treated with S-CRT versus S-RT had 55% survival advantage at 5 years (p < 0.05).
Conclusion
This study shows that adding adjuvant chemotherapy to S-RT improves survival outcomes in advanced OCSCC, especially in patients with ECS.
doi:10.1186/1916-0216-42-30
PMCID: PMC3651227  PMID: 23672952
12.  The impact of clinical versus pathological staging in oral cavity carcinoma–a multi-institutional analysis of survival 
Objectives
To evaluate any disparity in clinical versus pathological TNM staging in oral cavity squamous cell carcinoma (OCSCC) patients and any impact of this on survival.
Design
Demographic, survival, staging, and pathologic data on all patients undergoing surgical treatment for OCSCC in Alberta between 1998 and 2006 was collected. Clinical and pathological TNM staging data were compared. Patients were stratified as pathologically downstaged, upstaged or unchanged.
Setting
Tertiary care centers in Alberta, Canada.
Main outcome measures
Survival differences between groups were analyzed using Kaplan-Meier and Cox regression models.
Results
Patients with clinically early stage tumors were pathologically upstaged in 21.9% of cases and unchanged in 78.1% of cases. Patients with clinically advanced stage tumors were pathologically downstaged in 7.9% of cases and unchanged in 92.1% of cases. Univariate and multivariate estimates of disease-specific survival showed no statistically significant differences in survival when patients were either upstaged or downstaged.
Conclusions
Some disparity exists in clinical versus pathological staging in OCSCC, however, this does not have any significant impact on disease specific survival.
doi:10.1186/1916-0216-42-28
PMCID: PMC3651235  PMID: 23663449
13.  An Evaluation of Six Brief Interventions that Target Drug-Related Problems in Correctional Populations 
Finding brief effective treatments for criminal justice populations is a major public need. The CJ-DATS Targeted Intervention for Corrections (TIC), which consists of six brief interventions (Communication, Anger, Motivation, Criminal Thinking, Social Networks, and HIV/Sexual Health), were tested in separate federally-funded randomized control studies. In total, 1,573 criminal justice-involved individuals from 20 correction facilities participated (78% males; 54% white). Multi-level repeated measures analyses found significant gains in knowledge, attitudes, and psychosocial functioning (criteria basic to Knowledge, Attitude, and Practices (KAP) and TCU Treatment Process Models). While improvements were less consistent in criminal thinking, overall evidence supported efficacy for the TIC interventions.
doi:10.1080/10509674.2012.633020
PMCID: PMC3338318  PMID: 22547911
adaptive treatment; brief interventions; CJ-DATS; criminal justice treatment; TCU Treatment Model; tier one treatment
14.  Medication-Assisted Treatment in Criminal Justice Agencies Affiliated with the Criminal Justice-Drug Abuse Treatment Studies (CJ-DATS): Availability, Barriers & Intentions 
Substance Abuse  2012;33(1):9-18.
Medication-assisted treatment (MAT) is underutilized in the treatment of drug-dependent, criminal justice populations. This study surveyed criminal justice agencies affiliated with the Criminal Justice Drug Abuse Treatment Studies (CJ-DATS) to assess use of MAT and factors influencing use of MAT. A convenience sample (N=50) of criminal justice agency respondents (e.g., jails, prisons, parole/probation, and drug courts) completed a survey on MAT practices and attitudes. Pregnant women and individuals experiencing withdrawal were most likely to receive MAT for opiate dependence in jail or prison, while those re-entering the community from jail or prison were the least likely to receive MAT. Factors influencing use of MAT included criminal justice preferences for drug-free treatment, limited knowledge of the benefits of MAT, security concerns, regulations prohibiting use of MAT for certain agencies, and lack of qualified medical staff. Differences across agency type in the factors influencing use and perceptions of MAT were also examined.
MAT use is largely limited to detoxification and maintenance of pregnant women in criminal justice settings. Use of MAT during the community reentry period is minimal. Addressing inadequate knowledge and negative attitudes about MAT may increase its adoption, but better linkages to community pharmacotherapy during the reentry period might overcome other issues, including security, liability, staffing and regulatory concerns. The CJ-DATS collaborative MAT implementation study to address inadequate knowledge, attitudes and linkage will be described.
doi:10.1080/08897077.2011.611460
PMCID: PMC3295578  PMID: 22263709
15.  Desisting From Prescription Drug Abuse: An Application of Growth Models to Rx Opioid Users 
Journal of drug issues  2012;42(1):82-97.
Modern desistance research has examined many facets of desistance, in terms of theoretical predictors of desistance and recidivism, and in terms of differing types of offending. Though predicting desistance from illegal drug use is among these topics, no research to date has examined the predictors of desisting from prescription opioid abuse. This study uses longitudinal data from 318 prescription opioid users to analyze the effects of various predictors of desistance on declining nonmedical prescription opioid use, with an emphasis on gender differences among participants. Results indicate that theoretical and demographic characteristics correspond with differing rates of decline and further vary by gender.
doi:10.1177/0022042612436651
PMCID: PMC3378330  PMID: 22736809
Prescription drug abuse; opioids; desistance
16.  Microvascular Free Tissue Transfer in the Reconstruction of Scalp and Lateral Temporal Bone Defects 
Defects of the scalp and lateral temporal bone (LTB) represent a unique challenge to the reconstructive surgeon. Simple reconstructive methods such as skin grafts, locoregional flaps, or tissue expanders are often not feasible due to a myriad of reasons. Vascularized free tissue transfer coverage offers distinct advantages in managing these defects. A retrospective case series was performed on all patients at the University of Washington Medical Center who had scalp or LTB defects reconstructed with free tissue transfer from May 1996 to July 2009. Cases were analyzed for defect characteristics, flap type, vessel selection, radiation status, dural exposure, complications, and outcomes. Sixty-eight free flaps were performed in 65 patients with scalp or LTB defects. Twenty-two resections included craniotomy, and 48 patients had pre- or postoperative radiation. Defects ranged from 6 to 836 cm2. All flaps (46 latissimus, 11 rectus, 4 radial forearm, 6 anterolateral thigh, and 1 omental) were transferred successfully. Vein grafts were required in five cases. Complications included delayed flap failure requiring secondary reconstruction, neck hematoma, venous thrombosis, skull base infection, large wound dehiscence, small wound dehiscence, donor site hematoma and seroma, and cerebrospinal fluid leak. Cosmetic results were consistent and durable. Microvascular free tissue transfer is a safe, reliable method of reconstructing scalp and LTB defects and offers favorable cosmetic results. We favor the use of latissimus muscle-only flap with skin graft coverage for large scalp defects and rectus or anterolateral thigh free flaps for lateral temporal bone defects.
doi:10.1055/s-0031-1286119
PMCID: PMC3314257  PMID: 23205168
Scalp reconstruction; lateral temporal bone reconstruction; scalp neoplasms; scalp defects; microvascular reconstruction; free tissue transfer
17.  iSyTE: Integrated Systems Tool for Eye Gene Discovery 
Based on mouse lens gene expression profiling, a systems tool was developed for identification of genes associated with human congenital cataract. iSyTE ranked 88% of known isolated congenital cataract–associated genes within the top two of all candidates in the originally mapped genomic intervals.
Purpose.
To facilitate the identification of genes associated with cataract and other ocular defects, the authors developed and validated a computational tool termed iSyTE (integrated Systems Tool for Eye gene discovery; http://bioinformatics.udel.edu/Research/iSyTE). iSyTE uses a mouse embryonic lens gene expression data set as a bioinformatics filter to select candidate genes from human or mouse genomic regions implicated in disease and to prioritize them for further mutational and functional analyses.
Methods.
Microarray gene expression profiles were obtained for microdissected embryonic mouse lens at three key developmental time points in the transition from the embryonic day (E)10.5 stage of lens placode invagination to E12.5 lens primary fiber cell differentiation. Differentially regulated genes were identified by in silico comparison of lens gene expression profiles with those of whole embryo body (WB) lacking ocular tissue.
Results.
Gene set analysis demonstrated that this strategy effectively removes highly expressed but nonspecific housekeeping genes from lens tissue expression profiles, allowing identification of less highly expressed lens disease–associated genes. Among 24 previously mapped human genomic intervals containing genes associated with isolated congenital cataract, the mutant gene is ranked within the top two iSyTE-selected candidates in approximately 88% of cases. Finally, in situ hybridization confirmed lens expression of several novel iSyTE-identified genes.
Conclusions.
iSyTE is a publicly available Web resource that can be used to prioritize candidate genes within mapped genomic intervals associated with congenital cataract for further investigation. Extension of this approach to other ocular tissue components will facilitate eye disease gene discovery.
doi:10.1167/iovs.11-8839
PMCID: PMC3339920  PMID: 22323457
18.  An Evolutionarily Conserved Enhancer Regulates Bmp4 Expression in Developing Incisor and Limb Bud 
PLoS ONE  2012;7(6):e38568.
To elucidate the transcriptional regulation of Bmp4 expression during organogenesis, we used phylogenetic footprinting and transgenic reporter analyses to identify Bmp4 cis-regulatory modules (CRMs). These analyses identified a regulatory region located ∼46 kb upstream of the mouse Bmp4 transcription start site that had previously been shown to direct expression in lateral plate mesoderm. We refined this regulatory region to a 396-bp minimal enhancer, and show that it recapitulates features of endogenous Bmp4 expression in developing mandibular arch ectoderm and incisor epithelium during the initiation-stage of tooth development. In addition, this enhancer directs expression in the apical ectodermal ridge (AER) of the developing limb and in anterior and posterior limb mesenchyme. Transcript profiling of E11.5 mouse incisor dental lamina, together with protein binding microarray (PBM) analyses, allowed identification of a conserved DNA binding motif in the Bmp4 enhancer for Pitx homeoproteins, which are also expressed in the developing mandibular and incisor epithelium. In vitro electrophoretic mobility shift assays (EMSA) and in vivo transgenic reporter mutational analyses revealed that this site supports Pitx binding and that the site is necessary to recapitulate aspects of endogenous Bmp4 expression in developing craniofacial and limb tissues. Finally, Pitx2 chromatin immunoprecipitation (ChIP) demonstrated direct binding of Pitx2 to this Bmp4 enhancer site in a dental epithelial cell line. These results establish a direct molecular regulatory link between Pitx family members and Bmp4 gene expression in developing incisor epithelium.
doi:10.1371/journal.pone.0038568
PMCID: PMC3373496  PMID: 22701669
19.  A strategy for selecting sexual partners believed to pose little/no risks for HIV: Serosorting and its implications for HIV transmission 
AIDS care  2009;21(10):1279-1288.
A common HIV/AIDS risk reduction strategy among men who have sex with men (MSM) is to limit their unprotected sex partners to those who are of the same HIV status, a practice referred to as serosorting. Decisions to serosort for HIV risk reduction are based on personal impressions and beliefs, and there is limited guidance offered on this community derived strategy from public health services. This paper reviews research on serosorting for HIV risk reduction and offers an evidence-based approach to serosorting guidance. Following a comprehensive electronic and manual literature search, we reviewed 51 studies relating to the implications of serosorting. Studies showed that HIV negative MSM who select partners based on HIV status are inadvertently placing themselves at risk for HIV. Infrequent HIV testing, lack of HIV status disclosure, co-occurring STIs, and acute HIV infection impede the potential protective benefits of serosorting. Public health messages should continue to encourage reductions in numbers of sexual partners and increases in condom use. Risk reduction messages should also highlight the limitations of relying on one’s own and partner’s HIV status in making sexual risk decisions.
doi:10.1080/09540120902803208
PMCID: PMC2937200  PMID: 20024704
serosorting; acute infection; HIV testing; prevention messages
20.  Integrating an HIV/HCV Brief Intervention in Prisoner Reentry: Results of a Multisite Prospective Study 
Journal of psychoactive drugs  2008;40(4):427-436.
Brief interventions to reduce harmful or problem behaviors have become increasingly popular in a variety of health fields, including HIV and hepatitis risk reduction. A central issue in intervention research involves the evaluation of what constitutes an effective “dose” of an intervention. This research examines the relative effectiveness of three alternative brief interventions of varying intensity designed to change the risk behaviors of inmates who are reentering society: a DVD-based, peer delivered intervention; the NIDA Standard HIV Intervention; and a standard practice condition (HIV educational video). All participants randomly received one of the interventions and were tested for HIV and HCV prior to release from custody. Thirty and ninety-day follow-ups examined changes in high-risk behaviors. Results reported here for 343 subjects who have completed the 90–day follow up indicate significant reductions in reported sexual risk behaviors for those participating the DVD intervention, compared to the other two brief interventions. This study is among the first to report any positive impacts on sexual behaviors among a population of inmates returning to the community.
PMCID: PMC2725408  PMID: 19283947
drug abuse; HIV; inmates; intervention; prison
22.  Collaborative Behavioral Management for Drug-Involved Parolees: Rationale and Design of the Step'n Out Study 
This article describes the rationale, study design, and implementation for the Step'n Out study of the Criminal Justice Drug Abuse Treatment Studies. Step'n Out tests the relative effectiveness of collaborative behavioral management of drug-involved parolees. Collaborative behavioral management integrates the roles of parole officers and treatment counselors to provide role induction counseling, contract for pro-social behavior, and deliver contingent reinforcement of behaviors consistent with treatment objectives. The Step'n Out study will randomize 450 drug-involved parolees to collaborative behavioral management or usual parole. Follow-up at 3-and 9-months will assess primary outcomes of rearrest, crime and drug use. If collaborative behavioral management is effective, its wider adoption could improve the outcomes of community reentry of drug-involved ex-offenders.
doi:10.1080/10509670802134184
PMCID: PMC2756716  PMID: 19809591
Community corrections; community reinforcement; contingency management; drug abusear; graduated sanctions; parole
23.  Apology laws 
doi:10.1503/cmaj.1090007
PMCID: PMC2653588  PMID: 19289812
24.  Cutting Edge: Chemokine Receptor CCR4 Is Necessary for Antigen-Driven Cutaneous Accumulation of CD4 T Cells under Physiological Conditions1 
Dual expression of chemokine receptor CCR4 and E-selectin ligand is characteristic of skin-tropic CD4 T cells from blood, lymphoid organs, and the skin itself. A strong and specific correlation exists among CCR4, its ligand CCL17/TARC, and the cutaneous lymphocyte-homing process. Nevertheless, whether CCR4 function is required for skin-specific trafficking remains an open question, which we address in this study. We developed an Ag-specific, TCR-transgenic, murine CD4 T cell adoptive transfer model that induces a mixed Th1 and Th17 cutaneous response. Within the hosts, both CCR4+/+and CCR4−/− donor CD4 T cells contribute equally well to the circulating E-selectin ligand+ pool in response to Ag. However, only CCR4+/+ donor cells accumulate efficiently within the skin. CCR4−/− cells home normally to the peritoneum, showing that they do not have a general defect in lymphocyte trafficking. We conclude that under physiological conditions, CCR4 is a nonredundant, necessary component of skin-specific lymphocyte trafficking.
PMCID: PMC2575766  PMID: 17339428

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