An exploration of frontline health professional's current understanding of non-fatal strangulation.

AIM: To explore frontline health professionals' current understanding of non-fatal strangulation and their need for and support for a comprehensive education and screening package to support health delivery. DESIGN: A descriptive mixed-method approach was chosen to analyse responses to an anonymous, online survey consisting of ten Likert scale, open-ended and five demographic questions. 103 frontline health professionals (nurses, doctors, paramedics, midwives) participated in this study. METHODS: Content analysis of the Likert scale and open-ended questions describing the subjective experiences and perceptions of the participants was undertaken along with percentage and frequency counts of the rated Likert responses. RESULTS: The findings identified that 51.1% of health professionals do not ask about strangulation routinely and that 59% of health professionals reported receiving no formal education or professional development on NFS to enhance their knowledge or inform clinical practice. No health professionals identified mild traumatic brain injury as a consequence or sign of strangulation, nor did they identify an understanding that 50% of people may have no visible injuries after being strangled. Health professionals also do not routinely document the different agencies referred to or involved in supporting the person who experienced NFS. CONCLUSION: Findings suggest that frontline health professionals lack the confidence, skills and education needed to meet medical obligations to their patients and to fulfil their duty to 'do no harm'. Frontline health professionals would welcome a comprehensive education and screening package to guide recognition and response to non-fatal strangulation in their clinical settings. WHERE AND ON WHOM WILL THE RESEARCH HAVE AN IMPACT?: The purpose of the study was to understand and explore health professionals' knowledge about non-fatal strangulation so that improved education around better screening, and management of trauma-focused care to people who have been subjected to non-fatal strangulation could occur. NO PATIENT OR PUBLIC CONTRIBUTION: This review contains no patient or public contribution since it examines health professionals' knowledge of identifying non-fatal strangulation and the screening and assessment tools used in clinical practice.

Prognostic stratification of HPV-associated oropharyngeal cancer based on CD103+ immune cell abundance in patients treated on TROG 12.01 and De-ESCALaTE randomized trials.

BACKGROUND: High CD103+ intratumoral immune cell (ITIC) abundance is associated with better prognosis in unselected patients with human papilloma virus-associated oropharyngeal squamous cell carcinoma (HPV-associated OPSCC) treated with cisplatin and radiotherapy (CIS/RT). Substituting cetuximab (CETUX) for CIS with RT in HPV-associated OPSCC resulted in inferior efficacy. Our aim was to determine whether quantification of CD103 ITIC could be used to identify a population of HPV-associated OPSCC with superior prognosis. PATIENTS AND METHODS: We pooled data from the TROG 12.01 and De-ESCALaTE randomized trials that compared CETUX/70GyRT with CIS/70GyRT in low-risk HPV-associated OPSCC: American Joint Committee on Cancer 7 stage III (excluding T1-2N1) or stage IV (excluding N2b-c if smoking history >10 pack-years and/or distant metastases), including all patients with available tumor samples. The primary endpoint was failure-free survival (FFS) in patients receiving CETUX/RT comparing CD103+ ITIC high (≥30%) versus low (<30%). High and low CD103 were compared using Cox regression adjusting for age, stage and trial. RESULTS: Tumor samples were available in 159/182 patients on TROG 12.01 and 145/334 on De-ESCALaTE. CD103+ ITIC abundance was high in 27% of patients. The median follow-up was 3.2 years. The 3-year FFS in patients treated with CETUX/RT was 93% [95% confidence interval (CI) 79% to 98%] in high CD103 and 74% (95% CI 63% to 81%) in low CD103 [adjusted hazard ratio = 0.22 (95% CI 0.12-0.41), P < 0.001]. The 3-year overall survival in patients treated with CETUX/RT was 100% in high CD103 and 86% (95% CI 76% to 92%) in low CD103, P < 0.001. In patients treated with CIS/RT, there was no significant difference in FFS. CONCLUSIONS: CD103+ ITIC expression separates CETUX/RT-treated low-risk HPV-associated OPSCC into excellent and poor prognosis subgroups. The high CD103 population is a rational target for de-intensification trials.

Custom workflows to improve joint variant calling from multiple related tumour samples: FreeBayesSomatic and Strelka2Pass.

SUMMARY: This work describes two novel workflows for variant calling that extend the widely used algorithms of Strelka2 and FreeBayes to call somatic mutations from multiple related tumour samples and one matched normal sample. We show that these workflows offer higher precision and recall than their single tumour-normal pair equivalents in both simulated and clinical sequencing data. AVAILABILITY AND IMPLEMENTATION: Source code freely available at the following link: https://atlassian.petermac.org.au/bitbucket/projects/DAW/repos/multisamplevariantcalling and executable through Janis (https://github.com/PMCC-BioinformaticsCore/janis) under the GPLv3 licence. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Intracranial and extracranial efficacy of lorlatinib in patients with ALK-positive non-small-cell lung cancer previously treated with second-generation ALK TKIs.

BACKGROUND: Lorlatinib, a potent, brain-penetrant, third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), has substantial activity against ALK-positive non-small-cell lung cancer (NSCLC). This study assessed the overall, intracranial, and extracranial efficacy of lorlatinib in ALK-positive NSCLC that progressed on second-generation ALK TKIs. PATIENTS AND METHODS: In the ongoing phase II study (NCT01970865), patients with ALK-positive advanced NSCLC treated with ≥1 prior second-generation ALK TKI ± chemotherapy were enrolled in expansion cohorts (EXP) based on treatment history. Overall, intracranial and extracranial antitumor activity were assessed independently per modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. RESULTS: Of the 139 patients with ≥1 prior second-generation ALK TKI (EXP3B-5), 28 received one prior second-generation ALK TKI (EXP3B), 65 two prior ALK TKIs (EXP4), and 46 three prior ALK TKIs (EXP5). In EXP3B-5, the objective response rate (ORR) [95% confidence intervals] was 39.6% (31.4-48.2), intracranial ORR (IC-ORR) was 56.1% (42.4-69.3), extracranial ORR (EC-ORR) was 36.7% (28.7-45.3), median duration of response (DOR) was 9.6 months [5.6-16.7; IC-DOR, 12.4 (6.0-37.1); EC-DOR, 9.7 (6.1-33.3)], median progression-free survival was 6.6 (5.4-7.4) months, and median overall survival was 20.7 months (16.1-30.3). In EXP3B, the ORR was 42.9% (24.5-62.8), the IC-ORR was 66.7% (29.9-92.5), and the EC-ORR was 32.1% (15.9-52.4). In EXP4 and EXP5, the ORR was 38.7% (29.6-48.5), the IC-ORR was 54.2% (39.2-68.6), and the EC-ORR was 37.8% (28.8-47.5). CONCLUSIONS: Lorlatinib had clinically meaningful intracranial and extracranial antitumor activity in the post-second-generation ALK TKI setting, with elevated intracranial versus extracranial ORR, particularly in patients with fewer lines of therapy.

Clinical definition of acquired resistance to immunotherapy in patients with metastatic non-small-cell lung cancer.

Acquired resistance (AR) to programmed cell death protein 1/programmed death-ligand 1 [PD-(L)1] blockade is frequent in non-small-cell lung cancer (NSCLC), occurring in a majority of initial responders. Patients with AR may have unique properties of persistent antitumor immunity that could be re-harnessed by investigational immunotherapies. The absence of a consistent clinical definition of AR to PD-(L)1 blockade and lack of uniform criteria for ensuing enrollment in clinical trials remains a major barrier to progress; such clinical definitions have advanced biologic and therapeutic discovery. We examine the considerations and potential controversies in developing a patient-level definition of AR in NSCLC treated with PD-(L)1 blockade. Taking into account the specifics of NSCLC biology and corresponding treatment strategies, we propose a practical, clinical definition of AR to PD-(L)1 blockade for use in clinical reports and prospective clinical trials. Patients should meet the following criteria: received treatment that includes PD-(L)1 blockade; experienced objective response on PD-(L)1 blockade (inclusion of a subset of stable disease will require future investigation); have progressive disease occurring within 6 months of last anti-PD-(L)1 antibody treatment or rechallenge with anti-PD-(L)1 antibody in patients not exposed to anti-PD-(L)1 in 6 months.

Productivity and cost-effectiveness of short-rotation hardwoods on various land types in the southeastern USA.

Despite the growing need to produce energy crops, information on comprehensive feasibility of growing short-rotation woody crops (SRWCs) on non-contentious and less-utilized lands and lands transitioning from previous uses in the southeastern USA is limited. An assessment model (SRWC-PEAM) was developed and tested for assessing the feasibility of SRWCs on lands targeted for ecosystem-service enhancements based on land conditions, species, and stand and economic variables in the southeastern USA. Productivity and economic returns of sweetgum (Liquidambar styraciflua L.), sycamore (Platanus occidentalis L.), and poplar (Populus) stand differed due to land types, species' adaptability and biomass potential, and optimal land-type-based management schemes. Poplar stands had the greatest biomass and the highest returns on all land types although returns from the three species on most land types were poor using current reported regional delivered prices. Irrigating stands increased yields but returns were poorer than from non-irrigated stands due to high costs of irrigation. Longer rotations resulted in greater biomass and returns and were more crucial for irrigated stands. Significantly higher feedstock prices and productivities are requisite for SRWC viability in the southeastern USA. SRWC-PEAM is a web-based tool and can accommodate other SRWC species and assessment of environmental services associated with SRWCs.

Identification of an excellent prognosis subset of human papillomavirus-associated oropharyngeal cancer patients by quantification of intratumoral CD103+ immune cell abundance.

BACKGROUND: Accurate prognostic stratification of human papillomavirus-associated oropharyngeal cancers (HPV+OPSCC) is required to identify patients potentially suitable for treatment deintensification. We evaluated the prognostic significance of CD103, a surface marker associated with tissue-resident memory T cells (TRMs), in two independent cohorts of patients with HPV+OPSCC. PATIENTS AND METHODS: The abundance and distribution of CD103+ immune cells were quantified using immunohistochemistry in a cohort of 189 HPV+OPSCC patients treated with curative intent and correlated with outcome. Findings were then validated in an independent cohort comprising 177 HPV+OPSCCs using univariable and multivariable analysis. Intratumoral CD103+ immune cells were characterized by multispectral fluorescence immunohistochemistry and gene expression analysis. RESULTS: High intratumoral abundance of CD103+ immune cells using a ≥30% cut-off was found in 19.8% of tumors in the training cohort of HPV+OPSCC patients and associated with excellent prognosis for overall survival (OS) with adjusted hazard ratio (HR) of 0.13 [95% confidence interval (CI) 0.02-0.94, P = 0.004]. In the independent cohort of HPV+OPSCCs, 20.4% had high intratumoral CD103+ abundance and an adjusted HR for OS of 0.16 (95% CI 0.02-1.22, P = 0.02). Five year OS of patients with high intratumoral CD103 was 100% across both cohorts. The C-statistic for the multivariate prognostic model with stage and age was significantly improved in both cohorts with the addition of intratumoral CD103+ cell abundance. On the basis of spatial location, co-expression of CD8 and CD69, and gene expression profiles, intratumoral CD103+ cells were consistent with TRMs. CONCLUSION: Quantification of intratumoral CD103+ immune cell abundance provides prognostic information beyond that provided by clinical parameters such as TNM-staging, identifying a population of low risk HPV+OPSCC patients who are good candidates for trials of deintensification strategies.

Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001.

BACKGROUND: In the ongoing phase I PROFILE 1001 study, crizotinib showed antitumor activity in patients with ROS1-rearranged advanced non-small-cell lung cancer (NSCLC). Here, we present updated antitumor activity, overall survival (OS) and safety data (additional 46.2 months follow-up) for patients with ROS1-rearranged advanced NSCLC from PROFILE 1001. PATIENTS AND METHODS: ROS1 status was determined by FISH or reverse transcriptase-polymerase chain reaction. All patients received crizotinib at a starting dose of 250 mg twice daily. RESULTS: Fifty-three patients received crizotinib, with a median duration of treatment of 22.4 months. At data cut-off, treatment was ongoing in 12 patients (23%). The objective response rate (ORR) was 72% [95% confidence interval (CI), 58% to 83%], including six confirmed complete responses and 32 confirmed partial responses; 10 patients had stable disease. Responses were durable (median duration of response 24.7 months; 95% CI, 15.2-45.3). ORRs were consistent across different patient subgroups. Median progression-free survival was 19.3 months (95% CI, 15.2-39.1). A total of 26 deaths (49%) occurred (median follow-up period of 62.6 months), and of the remaining 27 patients (51%), 14 (26%) were in follow-up at data cut-off. Median OS was 51.4 months (95% CI, 29.3 to not reached) and survival probabilities at 12, 24, 36, and 48 months were 79%, 67%, 53%, and 51%, respectively. No correlation was observed between OS and specific ROS1 fusion partner. Treatment-related adverse events (TRAEs) were mainly grade 1 or 2, per CTCAE v3.0. There were no grade ≥4 TRAEs and no TRAEs associated with permanent discontinuation. No new safety signals were reported with long-term crizotinib treatment. CONCLUSIONS: These findings serve as a new benchmark for OS in ROS1-rearranged advanced NSCLC, and continue to show the clinically meaningful benefit and safety of crizotinib in this molecular subgroup. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT00585195.

Phase Ib study of atezolizumab combined with cobimetinib in patients with solid tumors.

BACKGROUND: Preclinical evidence suggests that MEK inhibition promotes accumulation and survival of intratumoral tumor-specific T cells and can synergize with immune checkpoint inhibition. We investigated the safety and clinical activity of combining a MEK inhibitor, cobimetinib, and a programmed cell death 1 ligand 1 (PD-L1) inhibitor, atezolizumab, in patients with solid tumors. PATIENTS AND METHODS: This phase I/Ib study treated PD-L1/PD-1-naive patients with solid tumors in a dose-escalation stage and then in multiple, indication-specific dose-expansion cohorts. In most patients, cobimetinib was dosed once daily orally for 21 days on, 7 days off. Atezolizumab was dosed at 800 mg intravenously every 2 weeks. The primary objectives were safety and tolerability. Secondary end points included objective response rate, progression-free survival, and overall survival. RESULTS: Between 27 December 2013 and 9 May 2016, 152 patients were enrolled. As of 4 September 2017, 150 patients received ≥1 dose of atezolizumab, including 14 in the dose-escalation cohorts and 136 in the dose-expansion cohorts. Patients had metastatic colorectal cancer (mCRC; n = 84), melanoma (n = 22), non-small-cell lung cancer (NSCLC; n = 28), and other solid tumors (n = 16). The most common all-grade treatment-related adverse events (AEs) were diarrhea (67%), rash (48%), and fatigue (40%), similar to those with single-agent cobimetinib and atezolizumab. One (<1%) treatment-related grade 5 AE occurred (sepsis). Forty-five (30%) and 23 patients (15%) had AEs that led to discontinuation of cobimetinib and atezolizumab, respectively. Confirmed responses were observed in 7 of 84 patients (8%) with mCRC (6 responders were microsatellite low/stable, 1 was microsatellite instable), 9 of 22 patients (41%) with melanoma, and 5 of 28 patients (18%) with NSCLC. Clinical activity was independent of KRAS/BRAF status across diseases. CONCLUSIONS: Atezolizumab plus cobimetinib had manageable safety and clinical activity irrespective of KRAS/BRAF status. Although potential synergistic activity was seen in mCRC, this was not confirmed in a subsequent phase III study. CLINICALTRIALS.GOV IDENTIFIER: NCT01988896 (the investigators in the NCT01988896 study are listed in the supplementary Appendix, available at Annals of Oncology online).

Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry.

BACKGROUND: Anti-PD1/PD-L1 directed immune checkpoint inhibitors (ICI) are widely used to treat patients with advanced non-small-cell lung cancer (NSCLC). The activity of ICI across NSCLC harboring oncogenic alterations is poorly characterized. The aim of our study was to address the efficacy of ICI in the context of oncogenic addiction. PATIENTS AND METHODS: We conducted a retrospective study for patients receiving ICI monotherapy for advanced NSCLC with at least one oncogenic driver alteration. Anonymized data were evaluated for clinicopathologic characteristics and outcomes for ICI therapy: best response (RECIST 1.1), progression-free survival (PFS), and overall survival (OS) from ICI initiation. The primary end point was PFS under ICI. Secondary end points were best response (RECIST 1.1) and OS from ICI initiation. RESULTS: We studied 551 patients treated in 24 centers from 10 countries. The molecular alterations involved KRAS (n = 271), EGFR (n = 125), BRAF (n = 43), MET (n = 36), HER2 (n = 29), ALK (n = 23), RET (n = 16), ROS1 (n = 7), and multiple drivers (n = 1). Median age was 60 years, gender ratio was 1 : 1, never/former/current smokers were 28%/51%/21%, respectively, and the majority of tumors were adenocarcinoma. The objective response rate by driver alteration was: KRAS = 26%, BRAF = 24%, ROS1 = 17%, MET = 16%, EGFR = 12%, HER2 = 7%, RET = 6%, and ALK = 0%. In the entire cohort, median PFS was 2.8 months, OS 13.3 months, and the best response rate 19%. In a subgroup analysis, median PFS (in months) was 2.1 for EGFR, 3.2 for KRAS, 2.5 for ALK, 3.1 for BRAF, 2.5 for HER2, 2.1 for RET, and 3.4 for MET. In certain subgroups, PFS was positively associated with PD-L1 expression (KRAS, EGFR) and with smoking status (BRAF, HER2). CONCLUSIONS: : ICI induced regression in some tumors with actionable driver alterations, but clinical activity was lower compared with the KRAS group and the lack of response in the ALK group was notable. Patients with actionable tumor alterations should receive targeted therapies and chemotherapy before considering immunotherapy as a single agent.

Correlation of extent of ALK FISH positivity and crizotinib efficacy in three prospective studies of ALK-positive patients with non-small-cell lung cancer.

Background: In clinical trials of patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) treated with crizotinib, evaluation of the relationship between the percentage of ALK-positive cells by fluorescence in situ hybridization (FISH)-particularly near the cut-off defining positive status-and clinical outcomes have been limited by small sample sizes. Patients and methods: Data were pooled from three large prospective trials (one single-arm and two randomized versus chemotherapy) of crizotinib in patients with ALK-positive NSCLC determined by Vysis ALK Break Apart FISH using a cut-off of ≥15% ALK-positive cells. Logistic regression and proportional hazards regression analyses were used to explore the association of percent ALK-positive cells with objective response and progression-free survival (PFS), respectively. Results: Of 11 081 screened patients, 1958 (18%) were ALK positive, 7512 (68%) were ALK negative, and 1540 (14%) were uninformative. Median percentage of ALK-positive cells was 58% in ALK-positive patients and 2% in ALK-negative patients. Of ALK-positive patients, 5% had 15%-19% ALK-positive cells; of ALK-negative patients, 2% had 10%-14% ALK-positive cells. Objective response rate for ALK-positive, crizotinib-treated patients with ≥20% ALK-positive cells was 56% (n = 700/1246), 55% (n = 725/1312) for those with ≥15% ALK-positive cells, and 38% for those with 15%-19% ALK-positive cells (n = 25/66). As a continuous variable, higher percentages of ALK-positive cells were estimated to be associated with larger differences in objective response and PFS between crizotinib and chemotherapy; however, tests for interaction between treatment and percentage of ALK-positive cells were not significant (objective response, P = 0.054; PFS, P = 0.17). Conclusions: Patients with ALK-positive NSCLC benefit from treatment with crizotinib across the full range of percentage of ALK-positive cells, supporting the clinical utility of the 15% cut-off. The small number of patients with scores near the cut-off warrant additional study given the potential for misclassification of ALK status due to technical or biologic reasons.

Development of a tool to measure women's perception of respectful maternity care in public health facilities.

BACKGROUND: Maternal mortality continues to be the biggest challenge facing Ethiopia and other developing countries. Although progress has been made in making maternity services available closer to the community, the rate of deliveries attended by skilled birth attendants has remained very low. Absence of respectful maternity care (RMC) is believed to have contributed to low utilization of facility delivery services. This study outlines steps undertaken to construct and validate a scale that measures women's perception of respectful maternity care provided in health facilities. METHODS: An inductive item generation process that included a literature review and in-depth interviews with labor and delivery clients, followed by an expert review, assured face validity and content validity of the tool. A draft RMC scale with 37 items and two additional measures of global satisfaction items, measured on a five-point Likert scale, were administered to a developmental sample of 509 postnatal care clients visiting facilities immediately after childbirth to 7 weeks postpartum. IBM SPSS 20 was used to perform exploratory factor analysis (EFA) using principal component analysis (PCA) with oblique rotation method. RESULTS: The final RMC scale with 15 items was loaded on four components. The extracted components were labeled as friendly care, abuse-free care, timely care, and discrimination-free care. The final RMC scale correlated strongly with the global satisfaction measures, indicating criterion-related validity of the scale. Content-related validity was assured by the process of item generation. Construct validity of the RMC scale was confirmed by high average factor loading of the four components ranging from 0.76 to 0.82 and low correlation between the components. Stability of the scale was confirmed by running PCA in a randomly selected split sample of 320 samples from the validation sample. The final 15-item scale showed an adequate reliability with α = 0.845. CONCLUSION: The 15-item RMC scale is a valid and reliable measure of women's perception of RMC received in health facilities. We recommend that health facilities use the RMC scale in urban public health facilities and that other researchers conduct further exploratory and confirmatory factor analysis in different geographic areas.

Frequency and prognostic significance of p16(INK4A) protein overexpression and transcriptionally active human papillomavirus infection in laryngeal squamous cell carcinoma.

BACKGROUND: Human papillomavirus (HPV) infection is a powerful prognostic biomarker in a subset of head and neck squamous cell carcinomas, specifically oropharyngeal cancers. However, the role of HPV in non-oropharyngeal sites, such as the larynx, remains unconfirmed. METHODS: We evaluated a cohort of 324 laryngeal squamous cell carcinoma (LSCC) patients for the expression of p16(INK4A) (p16) protein by immunohistochemistry (IHC) and for high-risk HPV E6 and E7 mRNA transcripts by RNA in situ hybridisation (ISH). p16 expression and HPV status were correlated with clinicopathological features and outcomes. RESULTS: Of 307 patients assessable for p16 IHC, 20 (6.5%) were p16 positive. Females and node-positive patients were more likely to be p16 positive (P<0.05). There were no other significant clinical or demographic differences between p16-positive and -negative cases. There was no difference in overall survival (OS) between p16-positive and -negative patients with 2-year survival of 79% in each group (HR=0.83, 95% CI 0.36-1.89, P=0.65). There was no statistically significant difference in failure-free survival (FFS) with 2-year FFS of 79% and 66% for p16-positive and -negative patients, respectively (HR=0.60, 95% CI 0.26-1.36, P=0.22). Only seven cases were found to be HPV RNA ISH positive, all of which were p16 IHC positive. There was no statistically significant difference in OS between patients with HPV RNA ISH-positive tumours compared with -negative tumours with 2-year survival of 86% and 71%, respectively (HR=0.76, 95% CI 0.23-2.5, P=0.65). The 2-year FFS was 86% and 59%, respectively (HR=0.62, 95% CI 0.19-2.03, P=0.43). CONCLUSIONS: p16 overexpression is infrequent in LSCC and the proportion of cases with high-risk HPV transcripts is even lower. There are no statistically significant correlations between p16 IHC or HPV RNA ISH status and OS or disease outcomes.

Outcomes of a Tailored Intervention for Cigarette Smoking Cessation Among Latinos Living With HIV/AIDS.

INTRODUCTION: Tobacco use has emerged as a leading killer among persons living with HIV, with effective approaches to tobacco treatment still unknown. HIV infection is nearly 3 times as prevalent in Latinos than in non-Latino Whites. This study reports the results of a randomized trial comparing a tailored intervention to brief counseling for smoking cessation among Latino smokers living with HIV (LSLWH). METHODS: LSLWH (N = 302; 36% female, 10% employed full-time, 49% born in United States) were randomized to 4 in-person sessions of a tailored intervention (Aurora) or 2 in-person sessions of brief advice (enhanced standard care [ESC]). Both groups received 8 weeks of nicotine replacement therapy (NRT) patch. Biochemically validated 6- and 12-month 7-day point-prevalence abstinence (PPA) rates were compared, along with secondary outcomes (e.g., reduction to light smoking, NRT adherence). RESULTS: Seven-day PPA rates reached 8% versus 11% at 6 months and 6% versus 7% at 12 months, for Aurora and ESC, respectively, with no between-group differences (p values > .40). Significant changes from baseline to 6 and 12 months among intervention targets were noted (percentage reduction in heavy smoking and dependence; increases in knowledge and self-efficacy). Baseline smoking frequency, older age, and higher intensity of patch use during the trial emerged as significant predictors of abstinence at 6 months. CONCLUSIONS: There was no evidence that the tailored intervention improved cessation rates. Interventions that encourage use of, and adherence to, empirically validated cessation aids require further development to reduce tobacco-related death and disease in this vulnerable population.

SRWC bioenergy productivity and economic feasibility on marginal lands.

Evolving bioenergy markets necessitate consideration of marginal lands for woody biomass production worldwide particularly the southeastern U.S., a prominent wood pellet exporter to Europe. Growing short rotation woody crops (SRWCs) on marginal lands minimizes concerns about using croplands for bioenergy production and reinforces sustainability of wood supply to existing and growing global biomass markets. We estimated mean annual aboveground green biomass increments (MAIs) and assessed economic feasibility of various operationally established (0.5 ha-109 ha) SRWC stands on lands used to mitigate environmental liabilities of municipal wastewater, livestock wastewater and sludge, and subsurface contamination by petroleum and pesticides. MAIs (Mg ha(-1) yr(-1)) had no consistent relationship with stand density or age. Non-irrigated Populus, Plantanus occidentalis L. and Pinus taeda L. stands produced 2.4-12.4 Mg ha(-1) yr(-1). Older, irrigated Taxodium distchum L., Fraxinus pennsylvanica L., and coppiced P. occidentalis stands had higher MAIs (10.6-21.3 Mg ha(-1) yr(-1)) than irrigated Liquidambar styraciflua L. and non-coppiced, irrigated P. occidentalis (8-18 Mg ha(-1) yr(-1)). Natural hardwood MAIs at 20-60 years were less than hardwood and P. taeda productivities at 5-20 years. Unlike weed control, irrigation and coppicing improved managed hardwood productivity. Rotation length affected economic outcomes although the returns were poor due to high establishment and maintenance costs, low productivities and low current stumpage values, which are expected to quickly change with development of robust global markets.

Pooling/bootstrap-based GWAS (pbGWAS) identifies new loci modifying the age of onset in PSEN1 p.Glu280Ala Alzheimer's disease.

The literature on GWAS (genome-wide association studies) data suggests that very large sample sizes (for example, 50,000 cases and 50,000 controls) may be required to detect significant associations of genomic regions for complex disorders such as Alzheimer's disease (AD). Because of the challenges of obtaining such large cohorts, we describe here a novel sequential strategy that combines pooling of DNA and bootstrapping (pbGWAS) in order to significantly increase the statistical power and exponentially reduce expenses. We applied this method to a very homogeneous sample of patients belonging to a unique and clinically well-characterized multigenerational pedigree with one of the most severe forms of early onset AD, carrying the PSEN1 p.Glu280Ala mutation (often referred to as E280A mutation), which originated as a consequence of a founder effect. In this cohort, we identified novel loci genome-wide significantly associated as modifiers of the age of onset of AD (CD44, rs187116, P=1.29 × 10⁻¹²; NPHP1, rs10173717, P=1.74 × 10⁻¹²; CADPS2, rs3757536, P=1.54 × 10⁻¹°; GREM2, rs12129547, P=1.69 × 10⁻¹³, among others) as well as other loci known to be associated with AD. Regions identified by pbGWAS were confirmed by subsequent individual genotyping. The pbGWAS methodology and the genes it targeted could provide important insights in determining the genetic causes of AD and other complex conditions.

Thromboprophylaxis for lung cancer patients--multimodality assessment of clinician practices, perceptions and decision support tools.

PURPOSE: The purpose of this study was to report the opinions and self-reported practices of clinicians, as well as the availability of decision support tools, regarding appropriate thromboprophylaxis for patients with lung cancer to identify variation in practice and/or divergence from evidence-based clinical practice guidelines (CPG). METHODS: A computer-generated survey (SurveyMonkey software) was distributed to surgical, radiation and medical oncologists with lung cancer specialisation, via membership of the Australian Lung Cancer Trials Group (ALTG) from May to September 2013. RESULTS: Seventy-two clinicians, from public, private, specialist and general hospitals, completed the survey (46% response rate). Hospital-endorsed CPG were widely available (91%); however, these routinely lacked robust recommendations for the ambulatory care setting (98%) and risk stratification tools (65%). Clinicians consistently identified ambulatory care treatment modalities (chemotherapy, alone or in combination with radiotherapy) as having similar (high) thrombotic risk as surgery. Timing and duration of pharmacological thromboprophylaxis prescribing among surgical oncologists varied and were divergent from guideline recommendations. Fifty-eight percent of surveyed clinicians cited a lack of high-quality data to guide preventative strategies in lung cancer patients. CONCLUSION: Clinicians consistently identified patients with lung cancer as having a high thromboembolic risk in both ambulatory and surgical settings, but with differences in recommendations and variation in practice. CPG lacked robust recommendations for the ambulatory care setting, the main arena for the multimodality lung cancer treatment paradigm.