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This article develops the concept of ‘deathlogging’ as a complement to the more popular ‘lifelogging’ to describe how wearable cameras record fatal accidents, particularly among action sports participants. The article situates deathlogging in a history of media and communication theory interested in the relationships between life and death, and in particular the concept of forensic mediation to describe technologies capable of documenting and reconstructing accidents. The wearable GoPro camera is a camera of choice for action sports athletes to easily record and share things like BASE jumping to gain audience views and capital in the form of sponsorships. Representative examples are discussed and analyzed to demonstrate how fatal accidents transform the value of GoPro footage from social-economic capital into forensic or juridical evidence to reconstruct accidents, make sense of fatalities, and, in some instances, argue for legal culpability. The article offers deathlogging as a concept which can be applied to a variety of recording situations with different kinds of wearable cameras.

Traditional siting of stomas, in the lower abdomen, has been guided by surgical dogma lacking evidence. In the lower abdomen, the combination of a thick and pendulous abdominal apron, can create a challenging and suboptimal site for a stoma. The anatomical determinant limiting delivery of a stoma to the abdominal skin is the distance of the SMA from the lower border of the pancreas. The aim of this cross-sectional study was to compare the distance between the traditional stoma site, and upper abdominal stoma sites, to both the superior mesenteric artery (SMA) origin and SMA at the inferior border of the pancreas on abdominal computed tomography (CT).A cross-sectional study at a single academic university hospital of adult patients who underwent abdominal CT in Australia.Two hundred and thirteen patients were included. Stoma sites in the upper abdomen were 57-76 mm shorter to the origin of the SMA and inferior border of the pancreas than those positioned at the traditional stoma site (P 0.001). The mean panniculus thickness in the upper abdomen was 10 mm thinner than in the lower abdomen and increased with increasing BMI (P 0.001). The ratio between the distance from the xiphisternum to umbilicus, and the umbilicus to pubic symphysis, was 1.10; this ratio increased with increasing BMI.The distance of the SMA to the skin is always shorter in the upper abdomen compared to the traditional stoma site. Consideration should be given to placing stomas in the upper abdomen, particularly in overweight or obese patients.

This paper explores the effects of a group-randomized controlled trial, Community Partners in Care (CPIC), on the development of interagency networks for collaborative depression care improvement between a community engagement and planning (CEP) intervention and a resources for services (RS) intervention that provided the same content solely via technical assistance to individual programs. Both interventions consisted of a diverse set of service agencies, including health, mental health, substance abuse treatment, social services, and community-trusted organizations such as churches and parks and recreation centers. Participants in the community councils for the CEP intervention reflected a range of agency leaders, staff, and other stakeholders. Network analysis of partnerships among agencies in the CEP versus RS condition, and qualitative analysis of perspectives on interagency network changes from multiple sources, suggested that agencies in the CEP intervention exhibited greater growth in partnership capacity among themselves than did RS agencies. CEP participants also viewed the coalition development intervention both as promoting collaboration in depression services and as a meaningful community capacity building activity. These descriptive results help to identify plausible mechanisms of action for the CPIC interventions and can be used to guide development of future community engagement interventions and evaluations in under-resourced communities.

NEPA is the first fixed‐combination antiemetic composed of the neurokinin‐1 receptor antagonist netupitant (netupitant; 300 mg) and the 5‐hydroxytryptamine‐3 receptor antagonist palonosetron (palonosetron; 0.50 mg). This study evaluated the pharmacokinetic profiles of netupitant and palonosetron. The pharmacokinetic profiles of both drugs were summarized using data from phase 1‐3 clinical trials. netupitant and palonosetron have high absolute bioavailability (63%‐87% and 97%, respectively). Their overall systemic exposures and maximum plasma concentrations are similar under fed and fasting conditions. netupitant binds to plasma proteins in a high degree (>99%), whereas palonosetron binds to a low extent (62%). Both drugs have large volumes of distribution (cancer patients: 1656‐2257 L and 483‐679 L, respectively). netupitant is metabolized by cytochrome P450 3A4 to 3 major pharmacologically active metabolites (M1, M2, and M3). palonosetron is metabolized by cytochrome P450 2D6 to 2 major substantially inactive metabolites (M4 and M9). Both drugs have similar intermediate‐to‐low systemic clearances and long half‐lives (cancer patients: netupitant, 19.5‐20.8 L/h and 56.0‐93.8 hours; palonosetron: 7.0‐11.3 L/h and 43.8‐65.7 hours, respectively). netupitant and its metabolites are eliminated via the hepatic/biliary route (87% of the administered dose), whereas palonosetron and its metabolites are mainly eliminated via the kidneys (85%‐93%). Altogether, these data explain the lack of pharmacokinetic interactions between netupitant and palonosetron at absorption, binding, metabolic, or excretory level, thus highlighting their compatibility as the oral fixed combination NEPA, with administration convenience that may reduce dosing mistakes and increase treatment compliance.

Background: Given national concern over rising mortality from opioid use disorders (OUD) and challenges to increasing OUD treatment access, a coalition approach may hold promise to improve access and out­comes for diverse populations. We present considerations of a community-partnered working group on adapting the Community Partners in Care (CPIC) study and coalition approach to OUD. Method: During January 2016 through Jan­uary 2017, academic, provider, consumer and policy stakeholders reviewed options to adapt CPIC’s Resources for Services (RS) for individual program technical assistance and Community Engagement and Planning (CEP) for coalition support to OUD treatments, integrating stakeholder input into design op­tions with estimated sample sizes. Findings: The working group recommend­ed Community Reinforcement and Family Treatment (CRAFT) as a stakeholder-support intervention to facilitate uptake and adher­ence to Medications for Addiction Treat­ment (MAT). Recommended implementa­tion interventions for MAT/CRAFT were expert technical assistance supplemented by organizational readiness, and CEP for coali­tion support with a Learning Collaborative. Power estimation suggests that to compare implementation intervention effects on abstinence would require a somewhat larger enrolled sample and 3-4 times the screening sample as CPIC, and for mortality, at least 5-10 times the enrolled sample as CPIC. Discussion: Stakeholders viewed the CPIC design and interventions as feasible and acceptable as community-wide approaches for addressing the opioid epidemic, but comparing impacts on mortality would require large, multi-site trials. Ethn Dis. 2018;28(Suppl 2):381-388; doi:10.18865/ed.28.S2.381.

Significance: Prior research suggests that Community Engagement and Planning (CEP) for coalition support compared with Re­sources for Services (RS) for program techni­cal assistance to implement depression quality improvement programs improves 6- and 12-month client mental-health related quality of life (MHRQL); however, effects for clients with multiple chronic medical condi­tions (MCC) are unknown. Objective: To explore effectiveness of CEP vs RS in MCC and non-MCC subgroups. Design: Secondary analyses of a cluster-randomized trial. Setting: 93 health care and community-based programs in two neighborhoods. Participants: Of 4,440 clients screened, 1,322 depressed (Patient Health Question­naire, PHQ8) provided contact information, 1,246 enrolled and 1,018 (548 with ≥3 MCC) completed baseline, 6- or 12-month surveys. Intervention: CEP or RS for implementing depression quality improvement programs. Outcomes and Analyses: Primary: depres­sion (PHQ9 ≥10), poor MHRQL (Short Form Health Survey, SF-12

Purpose To discuss new therapeutic strategies for chemotherapy-induced nausea and vomiting (CINV) involving 5-hydroxytryptamine type 3 (5HT3)-receptor antagonists (RAs). Summary CINV remains poorly controlled in patients receiving moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC); nausea and delayed-phase CINV (24-120 hours after chemotherapy) are the most difficult to control. National Comprehensive Cancer Network (NCCN) and American Society of Clinical Oncology (ASCO) antiemesis-guideline recommendations for HEC include a four-drug regimen (5HT3 RA, neurokinin 1 [NK1] RA, dexamethasone, and olanzapine). For some MEC regimens, a three-drug regimen (5HT3 RA, NK1 RA, and dexamethasone) is recommended. While 5HT3 RAs have dramatically improved CINV in the acute phase (0-24 hours after chemotherapy), their efficacy declines in the delayed phase. Newer formulations have been developed to extend 5HT3-RA efficacy into the delayed phase. Granisetron extended-release subcutaneous (GERSC), the most recently approved 5HT3 RA, provides slow, controlled release of therapeutic granisetron concentrations for ≥5 days. GERSC is included in the NCCN and ASCO guidelines for MEC and HEC, with NCCN-preferred status for MEC in the absence of an NK1 RA. Efficacy and safety of 5HT3 RAs in the context of guideline-recommended antiemetic therapy are reviewed. Conclusion Recent updates in antiemetic guidelines and the development of newer antiemet-ics should help mitigate CINV, this dreaded side effect of chemotherapy. GERSC, the most recently approved 5HT3-RA formulation, is indicated for use with other antiemetics to prevent acute and delayed nausea and vomiting associated with initial and repeat courses of MEC and anthracycline-cyclophosphamide combination-chemotherapy regimens.

ObjectiveThe effectiveness of community coalition building and program technical assistance was compared in implementation of collaborative care for depression among health care and community sector clients.MethodsIn under-resourced communities, within 93 programs randomly assigned to coalition building (Community Engagement and Planning) or program technical assistance (Resources for Services) models, 1,018 clients completed surveys at baseline and at six, 12, or 36 months. Regression analysis was used to estimate intervention effects and intervention-by-sector interaction effects on depression, mental health-related quality of life, and community-prioritized outcomes and on services use.ResultsFor outcomes, there were few significant intervention-by-sector interactions, and stratified findings suggested benefits of coalition building in both sectors. For services use, at 36 months, increases were found for coalition building in primary care visits, self-help visits, and appropriate treatment for community clients and in community-based services use for health care clients.ConclusionsRelative to program technical assistance, community coalition building benefited clients across sectors and shifted long-term utilization across sectors.

Background: Comorbid depression and substance use disorders (SUDs) are associated with poor health and social outcomes disproportionately affecting under-resourced communities. Objectives: To test the hypothesis that a coalition approach to collaborative care (CC) for depression would improve outcomes of hazardous drinking and behavioral health hospitalizations, relative to technical assistance, for individuals with comorbid substance use problems. Substance use problems were defined by meeting criteria for DSM-IV substance abuse or dependence, hazardous drinking by AUDIT-C, or treatment in a SUD program within the prior 6 months. Methods: Two depression CC implementation approaches were compared: Resources for Services (RS) provided expert technical support for CC toolkits to individual programs. Community engagement and planning (CEP) supported multi-sector coalitions in collaborating in planning, adapting, implementing and monitoring CC toolkits. One thousand eighteen individuals with depression (PHQ-8 ≥10) enrolled. Regression analyses estimated intervention effects in participants with comorbid substance use problems (n = 588, 281 females, 307 males). Substance use problems were defined by meeting criteria for DSM-IV substance abuse or dependence, hazardous drinking by AUDIT-C, or treatment in a SUD program within the prior 6 months. Results: There were no significant baseline differences by intervention status among participants with depression and substance use problems. Intervention effects on primary outcomes including depression were not significant at 6 months. Compared to RS, CEP significantly reduced alcohol consumption (CEP = 1.6, RS = 2.1, p = .038), probability of behavioral health hospitalizations (OR = 0.50, p = .036), and use of specialty mental health visits (IRR = 0.52, p = .027), while increasing use of faith-based depression services (IRR = 3.4, p = .001). Conclusions: Given feasibility and possible benefits, CEP should be considered a promising approach to implementing depression CC with potential benefits to adults with comorbid substance use problems.

The synthesis of [5]heterophenacenes bearing one or two indole, furan, or thiophene rings is described using an SNAr-anionic cyclization cascade strategy. The convergent reaction sequences furnish chryseno[1,2-b]heteroarenes and phenanthro[1,2-b:8,7-b']diheteroarenes in only four synthetic steps. The heteroaromatic functionality is selected and installed in the final step of the syntheses from common ortho-fluoro-ethynylarene precursors.

ObjectiveDepression and substance abuse are common among low-income adults from racial-ethnic minority groups who receive services in safety-net settings, although little is known about how clients differ by service setting. This study examined characteristics and service use among depressed, low-income persons from minority groups in underresourced communities who did and did not have a substance abuse history.MethodsThe study used cross-sectional baseline client data (N=957) from Community Partners in Care, an initiative to improve depression services in Los Angeles County. Clients with probable depression (eight-item Patient Health Questionnaire) from substance abuse programs were compared with depressed clients with and without a history of substance abuse from primary care, mental health, and social and community programs. Sociodemographic, health status, and services utilization variables were examined.ResultsOf the 957 depressed clients, 217 (23%) were from substance abuse programs; 269 (28%) clients from other sectors had a substance abuse history, and 471 (49%) did not. Most clients from substance abuse programs or with a substance abuse history were unemployed and impoverished, lacked health insurance, and had high rates of arrests and homelessness. They were also more likely than clients without a substance abuse history to have depression or anxiety disorders, psychosis, and mania and to use emergency rooms.ConclusionsClients with depression and a substance abuse history had significant psychosocial stressors and high rates of service use, which suggests that communitywide approaches may be needed to address both depression and substance abuse in this safety-net population.

Objective: With internal validity being a central goal of designed experiments, we seek to elucidate how community partnered participatory research (CPPR) impacts the internal validity of public health compara­tive-effectiveness research. Methods: Community Partners in Care (CPIC), a study comparing a community-coalition intervention to direct technical as­sistance for disseminating depression care to vulnerable populations, is used to illustrate design choices developed with attention to core CPPR principles. The study-design process is reviewed retrospectively and evaluated based on the resulting covariate balance across intervention arms and on broader peer-review assessments. Contribu­tions of the CPIC Council and the study’s design committee are highlighted. Results: CPPR principles contributed to building consensus around the use of randomization, creating a sampling frame, specifying geographic boundaries delimit­ing the scope of the investigation, grouping similar programs into pairs or other small blocks of units, collaboratively choosing random-number-generator seeds to deter­mine randomized intervention assignments, and addressing logistical constraints in field operations. Study protocols yielded samples that were well-balanced on background characteristics across intervention arms. CPIC has been recognized for scientific merit, has drawn attention from policy­makers, and has fueled ongoing research collaborations. Conclusions: Creative and collaborative fulfillment of CPPR principles reinforced the internal validity of CPIC, strengthening the study’s scientific rigor by engaging comple­mentary areas of knowledge and expertise among members of the investigative team. Ethn Dis. 2018;28(Suppl 2):357-364; doi:10.18865/ed.28.S2.357.

Objective: To compare community engage­ment and planning (CEP) for coalition support to implement depression quality improvement (QI) to resources for services (RS) effects on service-use costs over a 12-month period. Design: Matched health and community programs (N=93) were cluster-randomized within communities to CEP or RS. Setting: Two Los Angeles communities. Participants: Adults (N=1,013) with depressive symptoms (Patient Health Questionnaire (PHQ-8) ≥10); 85% African American and Latino. Interventions: CEP and RS to support pro­grams in depression QI. Main outcome measures: Intervention training and service-use costs over 12 months. Results: CEP planning and training costs were almost 3 times higher than RS, largely due to greater CEP provider training partici­pation vs RS, with no significant differences in 12-month service-use costs. Conclusions: Compared with RS, CEP had higher planning and training costs with simi­lar service-use costs. Ethn Dis. 2018;28(Sup­pl 2):349-356; doi:10.18865/ed.28.S2.349.

Guidelines for nonoperative management (NOM) of high-grade pancreatic injuries in children have not been established, and wide practice variability exists. The purpose of this study was to evaluate common clinical strategies across multiple pediatric trauma centers to develop a consensus-based standard clinical pathway.A multicenter, retrospective review was conducted of children with high-grade (American Association of Surgeons for Trauma grade III-V) pancreatic injuries treated with NOM between 2010 and 2015. Data were collected on demographics, clinical management, and outcomes.Eighty-six patients were treated at 20 pediatric trauma centers. Median age was 9 years (range, 1-18 years). The majority (73%) of injuries were American Association of Surgeons for Trauma grade III, 24% were grade IV, and 3% were grade V. Median time from injury to presentation was 12 hours and median ISS was 16 (range, 4-66). All patients had computed tomography scan and serum pancreatic enzyme levels at presentation, but serial enzyme level monitoring was variable. Pancreatic enzyme levels did not correlate with injury grade or pseudocyst development. Parenteral nutrition was used in 68% and jejunal feeds in 31%. 3Endoscopic retrograde cholangiopancreatogram was obtained in 25%. An organized peripancreatic fluid collection present for at least 7 days after injury was identified in 59% (42 of 71). Initial management of these included: observation 64%, percutaneous drain 24%, and endoscopic drainage 10% and needle aspiration 2%. Clear liquids were started at a median of 6 days (IQR, 3-13 days) and regular diet at a median of 8 days (IQR 4-20 days). Median hospitalization length was 13 days (IQR, 7-24 days). Injury grade did not account for prolonged time to initiating oral diet or hospital length; indicating that the variability in these outcomes was largely due to different surgeon preferences.High-grade pancreatic injuries in children are rare and significant variability exists in NOM strategies, which may affect outcomes and effective resource utilization. A standard clinical pathway is proposed.Therapeutic/care management, level V (case series).

Objective: Limited data exist on approaches to improve depression services for men in under-resourced communities. This article explores this issue using a sub-analysis of male participants in Community Partners in Care (CPIC). Design: Community partnered, cluster, randomized trial. Setting: Hollywood-Metropolitan and South Los Angeles, California. Participants: 423 adult male clients with modified depression (PHQ-8 score≥10). Interventions: Depression collaborative care implementation using community engagement and planning (CEP) across programs compared with the more-traditional individual program, technical assistance (Resources for Services, RS). Main Outcomes Measured: Depressive symptoms (PHQ-8 score), mental health-related quality of life (MHRQL), mental wellness, services utilization and settings. Results: At screening, levels of probable depression were moderate to high (17.5%- 47.1%) among men across services sectors. Intervention effects on primary outcomes (PHQ-8 score and MHRQL) did not differ. Men in CEP compared with RS had improved mental wellness (OR 1.85, 95% CI 1.00–3.42) and reduced hospitalizations (OR .40, 95% CI .16–.98), with fewer mental health specialty medication visits (IRR 0.33, 95% CI .15–.69), and a trend toward greater faith-based depression visits (IRR 2.89, 95% CI .99–8.45). Conclusions: Exploratory sub-analyses suggest that high rates of mainly minority men in under-resourced communities have high prevalence of depression. A multisector coalition approach may hold promise for improving community-prioritized outcomes, such as mental wellness and reduced hospitalizations for men, meriting further development of this approach for future research and program design.Ethn Dis. 2017;27(3):223-232; doi:10.18865/ed.27.3.223

Real-world treatment and monitoring patterns have not been well documented among imatinib-treated chronic phase chronic myeloid leukemia (CP-CML) patients. Thus, we evaluated these patterns and responses to imatinib in CP-CML patients.This retrospective study, based on the Georgia Cancer Specialists' electronic medical record (EMR) system, identified CP-CML patients initiating treatment with imatinib from 01/01/2002 to 11/01/2011 who were subsequently followed for ≥6 months.A total of 177 patients met the study criteria. Imatinib dose modification occurred in 59 patients (33%). Rates of treatment interruption, discontinuation, and switching to another therapy were 16%, 24%, and 23%, respectively. Of 27 patients discontinuing imatinib for lack of efficacy, 9 (33%) had initial dose escalation; 26 patients (96%) eventually switched to a second-generation tyrosine kinase inhibitor. By 3 months, 168 patients remained on imatinib, of whom 96 (57%) had undergone cytogenetic and/or molecular testing. The frequency of response monitoring fluctuated over time, with rates as high as 28% for cytogenetic and 69% for molecular testing. Cumulative response rates steadily increased; 18 month rates were 47% for complete cytogenetic response and 26% for major or complete molecular response. There were no cases of progression and/or death among 38 patients who were regularly monitored for molecular response within the first 12 months of imatinib. Ten of 98 patients (10%) not regularly monitored had progressed or died.Almost one-third of patients initiating imatinib for CP-CML required dose modification, treatment interruption, or discontinuation. Opportunities for improved monitoring in this setting were identified. Limitations include those inherent to retrospective analyses based on EMR and the uncertain extrapolability of the results.

BACKGROUND As medical homes are developing under health reform, little is known regarding depression services need and use by diverse safety-net populations in under-resourced communities. For chronic conditions like depression, primary care services may face new opportunities to partner with diverse community service providers, such as those in social service and substance abuse centers, to support a collaborative care model of treating depression.

BACKGROUND Depression contributes to disability and there are ethnic/racial disparities in access and outcomes of care. Quality improvement (QI) programs for depression in primary care improve outcomes relative to usual care, but health, social and other community-based service sectors also support clients in under-resourced communities. Little is known about effects on client outcomes of strategies to implement depression QI across diverse sectors. OBJECTIVE To compare the effectiveness of Community Engagement and Planning (CEP) and Resources for Services (RS) to implement depression QI on clients’ mental health-related quality of life (HRQL) and services use. DESIGN Matched programs from health, social and other service sectors were randomized to community engagement and planning (promoting inter-agency collaboration) or resources for services (individual program technical assistance plus outreach) to implement depression QI toolkits in Hollywood-Metro and South Los Angeles. PARTICIPANTS From 93 randomized programs, 4,440 clients were screened and of 1,322 depressed by the 8-item Patient Health Questionnaire (PHQ-8) and providing contact information, 1,246 enrolled and 1,018 in 90 programs completed baseline or 6-month follow-up. MEASURES Self-reported mental HRQL and probable depression (primary), physical activity, employment, homelessness risk factors (secondary) and services use. RESULTS CEP was more effective than RS at improving mental HRQL, increasing physical activity and reducing homelessness risk factors, rate of behavioral health hospitalization and medication visits among specialty care users (i.e. psychiatrists, mental health providers) while increasing depression visits among users of primary care/public health for depression and users of faith-based and park programs (each p p > 0.05). CONCLUSION Community engagement to build a collaborative approach to implementing depression QI across diverse programs was more effective than resources for services for individual programs in improving mental HRQL, physical activity and homelessness risk factors, and shifted utilization away from hospitalizations and specialty medication visits toward primary care and other sectors, offering an expanded health-home model to address multiple disparities for depressed safety-net clients.

Land‐use change is one of the biggest threats to biodiversity globally. The effects of land use on biodiversity manifest primarily at local scales which are not captured by the coarse spatial grain of current global land‐use mapping. Assessments of land‐use impacts on biodiversity across large spatial extents require data at a similar spatial grain to the ecological processes they are assessing. Here, we develop a method for statistically downscaling mapped land‐use data that combines generalized additive modeling and constrained optimization. This method was applied to the 0.5° Land‐use Harmonization data for the year 2005 to produce global 30″ (approx. 1 km2) estimates of five land‐use classes: primary habitat, secondary habitat, cropland, pasture, and urban. The original dataset was partitioned into 61 bio‐realms (unique combinations of biome and biogeographical realm) and downscaled using relationships with fine‐grained climate, land cover, landform, and anthropogenic influence layers. The downscaled land‐use data were validated using the PREDICTS database and the geoWiki global cropland dataset. Application of the new method to all 61 bio‐realms produced global fine‐grained layers from the 2005 time step of the Land‐use Harmonization dataset. Coarse‐scaled proportions of land use estimated from these data compared well with those estimated in the original datasets (mean R 2: 0.68 ± 0.19). Validation with the PREDICTS database showed the new downscaled land‐use layers improved discrimination of all five classes at PREDICTS sites (P

Results: The overall incidence of G-CSF use was 91%, with 73% of patients receiving primary G-CSF prophylaxis and 9% receiving secondary G-CSF prophylaxis. The incidence of FN was 5% of patients (31), with 71% of those 31 patients (22) experiencing FN in the first cycle of treatment. Grade 3 or 4 neutropenia occurred in 43% of patients, and neutropenia-related hospitalizations occurred in 4%. Overall, 88% of patients completed 4 cycles of TC therapy, and 89% had a relative dose intensity 85%. Conclusions: This is the largest community-based retrospective study to evaluate FN incidence in patients with ESBC who are treated with TC. The results suggest that G-CSF prophylaxis may be required to safely administer TC. When TC is administered with G-CSF prophylaxis, the rates of FN and clinically significant myelosuppression are similar to the rates for other taxanecontaining regimens used for ESBC.

Introduction Hypomethylating agents (HMAs) treat myelodysplastic syndromes (MDS) through suppression of abnormal clones that may cause low hemoglobin (Hgb), platelet (PLT) deficiencies, and reduced absolute neutrophil count (ANC). Our study examined hematologic outcomes in MDS among patients treated with HMAs in a large community hematology-oncology practice. Materials and Methods A retrospective study using electronic medical record data studied patients who received at least one cycle of a single HMA (decitabine [DAC] or azacitidine [AZA]) for MDS from June 1, 2006, to May 31, 2009, who had pretreatment and end-of-treatment Hgb, PLT counts, and ANC available. Multivariate logistic regression assessed predictors of end-of-treatment response (Hgb ≥ 11g/dL without transfusion or erythrocyte stimulating agent; PLT ≥ 100,000 cells/μL without transfusion; ANC ≥ 1000 cells/mm 3 without colony stimulating factor) adjusting for baseline laboratory values, age, gender, and comorbidities. HMA choice was studied as a predictor of outcome. Results A total of 137 patients (mean age, 72.2 years; 57% male) met full inclusion criteria (DAC = 84, AZA=53). Mean number of cycles was four (range, 1-16 cycles) for DAC and five (range, 1-23 cycles) for AZA. Total number of cycles significantly predicted Hgb, PLT, and ANC response (odds ratio [OR] 1.19, P = .029; OR 1.15, P = .031; OR 1.16, P = .047, respectively). Growth factor use at any point during HMA treatment was negatively associated with Hgb and ANC response (OR 0.85, P = .007; OR 0.96, P = .046). There was no difference between treatments in likelihood of PLT or ANC response. Conclusions Patients treated with HMAs for MDS are more likely to achieve hematologic response when treated with a greater number of cycles.

To assess the likelihood of subsequent chemotherapy-induced nausea and vomiting (CINV) events following a first chemotherapy administration CINV event in patients receiving single-day low, moderately, or highly emetogenic chemotherapy (LEC, MEC, or HEC).A retrospective analysis was conducted utilizing Georgia Cancer Specialists, Florida Cancer Specialists, and ACORN electronic medical records databases (April 2006 through July 2009). Patients were included who received more than one single-day LEC, MEC, or HEC administration (oral or intravenous) with no chemotherapy 3 months prior to the first LEC, MEC, or HEC administration. Two cohorts, patients with a first administration CINV and no first administration CINV, were created and followed for 6 months. A multivariate logistic regression assessed the likelihood of subsequent CINV, controlling for age, gender, Charlson comorbidity index, cancer type, number of chemotherapy administrations, gap between LEC, MEC, or HEC administrations, and number of different LEC, MEC, or HEC agents administered.A total of 10,586 patients met the inclusion criteria (LEC = 3099; MEC = 5172; HEC = 2315). Of those patients, 4.4% (n = 136), 7.8% (n = 402), and 13.8% (n = 320) experienced a CINV event with their initial single-day LEC, MEC, or HEC administration, respectively. The unadjusted subsequent CINV rate was higher in the cohorts with first LEC, MEC, or HEC administration CINV for all groups receiving LEC (33.1% vs. 16.0%; p 0.0001), MEC (46.5% vs. 18.9%; p 0.0001), or HEC (59.1% vs. 26.9%; p 0.0001). After controlling for covariates, patients with first LEC, MEC, or HEC administration CINV were 3.1, 3.8, and 3.7 times more likely to have a subsequent CINV compared to patients without a first LEC, MEC, or HEC administration CINV (Odds Ratio: 3.05 [95% CI: 2.08-4.48, p 0.0001]; 3.77 [95% CI: 3.04-4.68, p 0.0001]; and 3.70 [95% CI: 2.88-4.74, p 0.0001], respectively).In this retrospective analysis, patients receiving single-day LEC, MEC, or HEC who had a prior CINV were at increased risk of subsequent CINV. Further studies assessing increased risk of a subsequent CINV events are warranted given this study represents an assessment of electronic medical record data within select community-based populations under usual care.

The purpose of this study is to examine the risk of uncontrolled chemotherapy-induced nausea/vomiting (CINV) among lung cancer patients receiving multi-day chemotherapy and ondansetron- or palonosetron-initiated prophylactic antiemetic regimens in a community oncology setting. The Georgia Cancer Specialists electronic medical records database was used to retrospectively identify lung cancer patients who received multi-day cisplatin or carboplatin regimens with ondansetron or palonosetron on day 1 between April 1, 2006 and July 31, 2009. Uncontrolled CINV events were identified through ICD-9-CM codes (nausea/vomiting), CPT codes (dehydration), rescue medications, nausea/vomiting hospitalizations, and/or antiemetic therapy after last chemotherapy administration of the cycle. Risk for uncontrolled CINV, up to 7 days after last chemotherapy administration, was analyzed at cycle level using logistic regression with regressors of gender, age, number of chemotherapy administration days, Charlson comorbidity index, cancer type, multicancer diagnoses, and chemotherapy regimen. A total of 209 palonosetron and 153 ondansetron patients (702 and 515 cycles, respectively) met the inclusion criteria. Palonosetron patients were significantly older (mean 67.9 versus 63.9 years; P

Background Criteria for adoption of new therapies and treatment paradigms in community oncology practices can differ substantively from that of academic medical centers. Differences arise, in part, from the influence of patient mix, available resources and services offered, physician/staff experiences, and the adherence to uniform treatment guidelines. Georgia Cancer Specialists (GCS) is a 31-site community-based group practice with 41 hematologists/oncologists motivated to standardize medical decision-making and optimize patient outcomes and health-care resource utilization. Patients and Methods Using our integrated electronic medical records and billing database (OASIS), we conducted a retrospective evaluation to assess the impact of 3 new agents (decitabine, 5-azacitidine, and lenalidomide) on practice patterns and outcomes in an elderly population with myelodysplastic syndrome (MDS) in the community setting. From January 2006 to June 2007, data from 1161 patients with MDS (mean age, 71 years; 63% women; 60% Medicare/Medicaid recipients) were collected. Of these, 76 patients (6.5%) received ≥ 1 MDS-indicated therapeutic agent (47% decitabine, 32% 5-azacitidine, 46% lenalidomide; 25% received ≥ 2 agents) for a median of 3, 2, and 3 cycles, respectively. Results In general, the data suggest that patients receiving MDS-therapeutic agents had hematologic improvement and experienced reductions in transfusion requirements. The GCS population and treatment-related data reflect the uptake of new MDS therapeutic agents introduced proactively into a real-world community oncology practice and supplements information from randomized clinical trials. Conclusion Data derived from the community setting have the potential to provide important insights about actual disease prevalence, patient demographics, factors that influence medical careseeking, clinical management, and outcomes outside of academic institutions.

ObjectiveCommunity engagement and planning (CEP) could improve dissemination of depression care quality improvement in underresourced communities, but whether its effects on provider training participation differ from those of standard technical assistance, or resources for services (RS), is unknown. This study compared program- and staff-level participation in depression care quality improvement training among programs enrolled in CEP, which trained networks of health care and social-community agencies jointly, and RS, which provided technical support to individual programs.MethodsMatched programs from health care and social-community service sectors in two communities were randomly assigned to RS or CEP. Data were from 1,622 eligible staff members from 95 enrolled programs. Primary outcomes were any staff trained (for programs) and total hours of training (for staff). Secondary staff-level outcomes were hours of training in specific depression collaborative care components.ResultsCEP programs were more likely than RS programs to participate in any training (p=.006). Within health care sectors, CEP programs were more likely than RS programs to participate in training (p=.016), but within social-community sectors, there was no difference in training by intervention. Among staff who participated in training, mean training hours were greater among CEP programs versus RS programs for any type of training (p

The accumulation of 3-methylindole (3MI) in uncastrated male pigs (boars) is a major cause of boar taint, which negatively affects the quality of meat from the animal. Previously, CYP2E1 and CYP2A have been identified as cytochrome P450 (P450) isoforms involved in the metabolism of 3MI using porcine liver microsomes. This study further examines the role of these isoforms in the metabolism of 3MI using a primary porcine hepatocyte model by examining metabolic profiles of 3MI after incubation with P450 inhibitors. Incubation of hepatocytes with 4-methylpyrazole resulted in a selective inhibition of CYP2E1 activity as determined by p-nitrophenol hydroxylase activity and an associated significant decrease in the production of the 3MI metabolites 3-hydroxy-3-methyloxindole and 3-methyloxindole. Furthermore, inhibition of CYP2A, as assayed by coumarin 7-hydroxylase activity, using 8-methoxypsoralen and diethyldithiocarbamate was not associated with any further significant inhibition of the production of 3MI metabolites. Treatment with general P450 inhibitors resulted in further decreases in CYP2E1 activity and a more dramatic decrease in the production of 3MI metabolites, suggesting that additional P450s may be involved in the phase 1 metabolism of 3-methylindole. In conclusion, CYP2E1 activity levels are more important than CYP2A activity levels for the metabolism of 3-methylindole in isolated pig hepatocytes.

A significant portion of the domestic bio-research base-and the one most likely to provide translational research-is not engaged in biodefense. Despite the fact that more than one-third of all life science researchers are employed in commercial bio-research, fewer than 3% of the 1,500 U.S. bio-technology companies are involved in biosecurity initiatives. The bio-tech industry has largely not aligned itself to play an integral role in biosecurity, but there are a few policy changes that could dramatically alter this balance. These include engaging and motivating the bio-technology middle class, seeding secondary markets, focusing on system solutions, providing reagents and standards, aligning communications, and prioritizing translational research. By reaching out, policymakers can span the current chasm between the bio-industry and government, build a stable biodefense industrial base, establish solid working relationships, and secure better services and products. The rewards would be significant for government and industry alike.

We present calculations of the stochastic gravitational wave (GW) background result- ing from neutron star birth throughout the Universe. We update previous calculations by employing three GW waveforms from Dimmelmeier, Font & Muller (2002), based on three models incorporating general relativistic eects for the axisymmetric core col- lapse of rotating massive stars. Source-rate evolution is accounted for by using a sim- ulated star formation rate model based on a 'flat-⁄' cosmology (Hernquist & Springle 2003). We show that the GW background is only weakly dependent on the source-rate evolution model. Prominent features in the single-source GW spectral strain can be related to the calculated background spectra, even though the features are broadened and redshifted because of contributions from high-redshift sources. The background spectral closure density is reduced by 1-2 orders of magnitude compared to previous calculations, a consequence of using relativistic single-source GW waveforms and a more slowly evolving source-rate density. Duty cycle estimates for this background imply a non-continuous signal, assuming it consists predominantly of 'regular' and 'rapid' core-collapse models. We note that the background may be considerably en- hanced by the inclusion of dynamic post-collapse instabilities (bar-modes), which are not included in this work, so our estimates for this background may be lower limits.

Ruminants fed high-grain diets often are subjected to ruminal acidosis, which can lead to excessive absorption of lactate into the blood stream, thereby causing metabolic acidosis. Metabolic acidosis leads to body protein loss, mainly due to increased skeletal muscle degradation. Our objective was to determine the effects of metabolic acidosis on the messenger RNA (mRNA) abundance of genes encoding components of the ubiquitin-mediated proteolytic pathway in the skeletal muscle of lactating Holstein cows. Cows (n = 20) were assigned to one of two treatments: 1) control; or 2) NutriChlor 18-8, an HCl-treated supplement, which was fed to induce chronic metabolic acidosis. The longissimus muscle was biopsied before and after 10 d of treatments. Total RNA isolated from muscle tissue was hybridized with (32)P-labeled cDNA probes encoding for 14-kDa ubiquitin carrier protein E2 (14-kDa E2), ubiquitin, and C8 and C9 subunits of the 20S proteasome. Induction of metabolic acidosis increased (P0.05) skeletal muscle mRNA levels for ubiquitin (25%), 14-kDa E2 (34%), and the C8 subunit (20%); however, mRNA abundance for the C9 subunit was unaffected (P0.05). These results suggest that up-regulation of the ubiquitin-proteasome pathway is the mechanism by which metabolic acidosis stimulates muscle wasting in ruminants.

Murine hepatic cytochrome P450 2A5 (CYP2A5) is uniquely induced by a variety of agents that cause liver injury and inflammation, conditions that are typically associated with downregulation of P450s. We hypothesized that induction of CYP2A5 occurs in response to hepatocellular damage resulting in endoplasmic reticulum (ER) stress. Treatment of mice in vivo and mouse hepatocytes in primary culture with the CYP2A5 inducer pyrazole resulted in overexpression of the ER stress biomarker glucose-regulated protein (GRP) 78. Treatment of primary hepatocytes with ER stress activators thapsigargin, tunicamycin, and trans-4,5-dihydroxy-1,2-dithiane (DTT(ox)) and the calcium ionophore A23187 (calcimycin) resulted in elevated GRP78 mRNA levels; however, only the reducing agent DTT(ox) induced levels of CYP2A5 mRNA, protein, and coumarin 7-hydroxylase activity. To test the hypothesis that CYP2A5 induction is due to liver injury resulting from altered cellular redox status, we demonstrated that CYP2A5 induction, elevated serum alanine aminotransferase, and oxidative protein damage occur concurrently in pyrazole-treated mice. Pyrazole also induced the expression of cytosolic alpha and mu class glutathione S-transferase expression both in vivo and in primary mouse hepatocytes. Moreover, treatment of hepatocytes with the redox cycling quinone menadione resulted in overexpression of CYP2A5 and GSTM1 mRNA. Finally, pretreatment of hepatocytes with the antioxidants N-acetylcysteine and vitamin E attenuated pyrazole-mediated increases in CYP2A5 mRNA levels. These findings clearly indicate that induction of mouse hepatic CYP2A5 during liver injury occurs via a novel mechanism involving ER stress due to altered cellular redox status.

The influence of pro-inflammatory cytokines on alpha class glutathione S-transferase A1 and A2 (GSTA1/A2) expression was examined in human colonic epithelial cells (Caco-2) in culture. Dose-dependent reductions in GSTA1/A2 mRNA, protein, and activity levels occurred in Caco-2 cells cultured in conditioned medium (CM) from lipopolysaccharide-stimulated murine monocyte-macrophage cells (RAW 264.7). Neutralizing anti-interleukin-1beta (IL-1beta) antibodies attenuated this repression of GSTA1/A2 expression by CM. Moreover, recombinant human IL-1beta reduced GSTalpha expression at the mRNA, protein, and activity levels in a dose-related fashion. Reduction of GSTA1/A2 mRNA levels by IL-1beta was attenuated by pretreatment with IL-1 receptor antagonist. GSTA1/A2 mRNA half-lives were similar in control and IL-1beta-treated cells, indicating that IL-1beta has no effect on mRNA stability. In reporter gene studies, IL-1beta caused a dose-related reduction of luciferase activity in Caco-2 cells transfected with the full-length GSTA1 promoter-luciferase construct. Using truncated constructs, IL-1beta responsiveness was mapped to a region 286 base pairs upstream to the coding region. Deletion of a hepatic nuclear factor 1 (HNF-1) site in this region abrogated the IL-1beta-mediated repression of GSTA1 promoter activity. These results demonstrate that IL-1beta down-regulates GSTA1/A2 expression in cultured human enterocytes by a transcriptional mechanism involving an HNF-1 site.

The adaptive immune system induces T cells to change from a naive phenotype to a Th1/Th2 phenotype each of which produce characteristic types of cytokines. Knowledge of whether a specific immune response is Th1 or Th2 is a useful indicator for diseases with basis in immune function disorder. An assay that can rapidly analyze multiple cytokines indicative of these two cell types from small sample quantities can be an extremely useful research and diagnostic tool. Silanized glass slides were printed with multiple arrays of capture antibodies to detect eight different cytokines involved in the Th1/Th2 response along with control proteins for assessing assay performance. Arrays were developed by sequential addition of known antigen amounts, detector antibodies and a fluorescent detection system followed by imaging and quantification. These arrays were used to determine the specificity, sensitivity and reproducibility of the assay and the performance compared with conventional ELISA. This multiplexed assay is able to measure human Th1/Th2 cytokines in sample volumes lower than 20 microl. The assay sensitivity for the eight cytokines range from 0.3 microg/l for IL-4 to 6.4 microg/l for IL-5 which are either comparable to or higher than those reported for conventional ELISA or bead-based multiplex ELISA methods. This assay can be automated to measure expression levels of multiple Th1/Th2 cytokines simultaneously from tens to hundreds of biological samples. This assay platform is more sensitive and has a larger dynamic range as compared to a conventional ELISA in addition to significantly reducing the time and cost of assay. This platform provides a versatile system to rapidly quantify a wide variety of proteins in a multiplex format.

Hepatic expression of cytochrome P450 2A6 (CYP2A6) varies widely in humans and is induced during hepatitis; however, the mechanism regulating CYP2A6 has not been established. The murine orthologue Cyp2a5 is regulated post-transcriptionally by mRNA stabilization. A 43-kDa protein that binds to the 3'-untranslated region (3'-UTR) of Cyp2a5 mRNA has been identified, but its role in mRNA stabilization is unclear. We hypothesized that similar interactions occur between cytosolic proteins in human liver and CYP2A6 3'-UTR mRNA. We identified, by RNA electrophoretic mobility shift assay, an hepatic cytosolic protein that binds specifically to sequences in the 3'-UTR of CYP2A6. Complexes did not form with denatured proteins and were eliminated with proteinase K digestion. Complex formation was inhibited with a molar excess of unlabeled CYP2A6 RNA but not by non-specific competitor RNA. Protein-mRNA interactions were not affected by probe denaturation, suggesting that RNA secondary structure is not essential for binding. UV cross-linking of complexes revealed RNA-binding proteins in both human and mouse liver cytosols with molecular masses of approximately 43 kDa. Using truncated RNA probes corresponding to various lengths of CYP2A6 mRNA, the protein-binding site was localized to a 50-nucleotide region between bases 1478 and 1527 of the 3'-UTR. Complex formation with hepatic cytosolic protein from four human subjects correlated with levels of hepatic CYP2A6 microsomal protein, suggesting a possible regulatory role. Further characterization of the RNA-binding protein, the primary binding site, and the influence of this interaction on CYP2A6 mRNA stability will help to elucidate the relevance of these findings to the post-transcriptional control of CYP2A6.

Summary cDNA microarrays containing 1443Arabidopsis thalianagenes were analyzed for expression profiles in major organs ofArabidopsisplants. Novel expression profiles were identified for many coding sequences with putative gene identifications. Expression patterns of novel sequences provided clues to their possible functions. The results demonstrate how microarrays containing a large number ofArabidopsisgenes can provide a powerful tool for plant gene discovery, functional analysis and elucidation of genetic regulatory networks.

cDNA microarray technology is used to profile complex diseases and discover novel disease-related genes. In inflammatory disease such as rheumatoid arthritis, expression patterns of diverse cell types contribute to the pathology. We have monitored gene expression in this disease state with a microarray of selected human genes of probable significance in inflammation as well as with genes expressed in peripheral human blood cells. Messenger RNA from cultured macrophages, chondrocyte cell lines, primary chondrocytes, and synoviocytes provided expression profiles for the selected cytokines, chemokines, DNA binding proteins, and matrix-degrading metalloproteinases. Comparisons between tissue samples of rheumatoid arthritis and inflammatory bowel disease verified the involvement of many genes and revealed novel participation of the cytokine interleukin 3, chemokine Groα and the metalloproteinase matrix metallo-elastase in both diseases. From the peripheral blood library, tissue inhibitor of metalloproteinase 1, ferritin light chain, and manganese superoxide dismutase genes were identified as expressed differentially in rheumatoid arthritis compared with inflammatory bowel disease. These results successfully demonstrate the use of the cDNA microarray system as a general approach for dissecting human diseases.

A low-power 60 GHz gyrotron collective Thomson scattering diagnostic has been operating on TFTR to test the feasibility of detecting alpha particles when scattering perpendicular to the magnetic field. An enhanced scattered signal is predicted to result from the interaction of the energetic ions with plasma resonances in the lower hybrid frequency range. Millimeter-wave power levels at the plasma were approximately 200 W for typical pulse lengths of 50 ms. Deuterium and possible fusion product ion cyclotron frequencies and their harmonics were observed during neutral beam heating. These spectra are similar to ion cyclotron emission spectra which are detected with radio-frequency probes on TFTR at the plasma edge. Also, ion cyclotron resonance heating fundamental and harmonic fluctuations were observed. However, a signal has not been definitively detected in the lower hybrid frequency range which correlates to alpha particles. Broadband noise was observed during neutral beam heating which is greater than t...

e18280Background: Peripheral T-Cell Lymphoma (PTCL) is a rare, aggressive form of non-hodgkin lymphoma. Initial treatment consists of conventional chemotherapy regimens; although novel therapies fo...

e18279Background: PTCL is a difficult to treat, heterogeneous form of non-Hodgkins Lymphoma. Traditional B-cell lymphoma regimens (tBCLr) have been adapted for use in PTCL but have shown low respon...