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Objective: The prevalence of mental illness among those in prison is much higher than in the community; however, very few studies have examined whether rates have changed over time, in line with increasing self-reported rates in the community. Methods: This study compares the prevalence of self-reported mental illness, self-harm and suicidal thoughts/behaviours, and drug and alcohol use across three waves (2001, 2009 and 2015) of health surveys involving men and women in New South Wales prisons and compared these rates with published community-level findings. Results: The prevalence of those reporting any mental health diagnosis increased significantly across the three surveys, even after adjustment for socio-demographic and criminal justice variables that also changed over time. Individuals surveyed in 2015 were more likely to report a mental health diagnosis than those surveyed in 2001 (adjusted odds ratio = 2.66, 95% confidence interval = [2.16, 3.27]). The prevalence of self-harm and suicidal thoughts and behaviours remained stable across the three surveys, while self-reported regular drug use decreased over the period. Women experienced a far greater burden of mental illness than men across all three surveys and experienced more growth in the prevalence of most psychiatric disorders. Conclusion: These findings have important implications for public and prison health systems given the poor social, health and criminal justice outcomes of those imprisoned with mental illness, both in custody and post-release.

In the lower troposphere, rapid collisions between ions and trace gases result in the transfer of positive charge to the highest proton affinity species and negative charge to the lowest proton affinity species. Measurements of the chemical composition of ambient ions thus provide direct insight into the most acidic and basic trace gases and their ion–molecule clusters – compounds thought to be important for new particle formation and growth. We deployed an atmospheric pressure interface time-of-flight mass spectrometer (APi-ToF) to measure ambient ion chemical composition during the 2016 Holistic Interactions of Shallow Clouds, Aerosols, and Land Ecosystems (HI-SCALE) campaign at the United States Department of Energy Atmospheric Radiation Measurement facility in the Southern Great Plains (SGP), an agricultural region. Cations and anions were measured for alternating periods of ∼ 24 h over 1 month. We use binned positive matrix factorization (binPMF) and generalized Kendrick analysis (GKA) to obtain information about the chemical formulas and temporal variation in ionic composition without the need for averaging over a long timescale or a priori high-resolution peak fitting. Negative ions consist of strong acids including sulfuric and nitric acid, organosulfates, and clusters of NO3- with highly oxygenated organic molecules (HOMs) derived from monoterpene (MT) and sesquiterpene (SQT) oxidation. Organonitrates derived from SQTs account for most of the HOM signal. Combined with the diel profiles and back trajectory analysis, these results suggest that NO3 radical chemistry is active at this site. SQT oxidation products likely contribute to particle growth at the SGP site. The positive ions consist of bases including alkyl pyridines and amines and a series of high-mass species. Nearly all the positive ions contained only one nitrogen atom and in general support ammonia and amines as being the dominant bases that could participate in new particle formation. Overall, this work demonstrates how APi-ToF measurements combined with binPMF analysis can provide insight into the temporal evolution of compounds important for new particle formation and growth.

Supplementary Table 2 from Activated Phosphoinositide 3-Kinase/AKT Signaling Confers Resistance to Trastuzumab but not Lapatinib

Supplementary Table 1 from Activated Phosphoinositide 3-Kinase/AKT Signaling Confers Resistance to Trastuzumab but not Lapatinib

Trastuzumab and lapatinib provide clinical benefit to women with human epidermal growth factor receptor 2 (HER)–positive breast cancer. However, not all patients whose tumors contain the HER2 alteration respond. Consequently, there is an urgent need to identify new predictive factors for these agents. The aim of this study was to investigate the role of receptor tyrosine kinase signaling and phosphoinositide 3-kinase (PI3K)/AKT pathway activation in conferring resistance to trastuzumab and lapatinib. To address this question, we evaluated response to trastuzumab and lapatinib in a panel of 18 HER2-amplified cell lines, using both two- and three-dimensional culture. The SUM-225, HCC-1419, HCC-1954, UACC-893, HCC-1569, UACC-732, JIMT-1, and MDA-453 cell lines were found to be innately resistant to trastuzumab, whereas the MDA-361, MDA-453, HCC-1569, UACC-732, JIMT-1, HCC-202, and UACC-893 cells are innately lapatinib resistant. Lapatinib was active in de novo (SUM-225, HCC-1419, and HCC-1954) and in a BT-474 cell line with acquired resistance to trastuzumab. In these cells, trastuzumab had little effect on AKT phosphorylation, whereas lapatinib retained activity through the dephosphorylation of AKT. Increased phosphorylation of HER2, epidermal growth factor receptor, HER3, and insulin-like growth factor IR correlated with response to lapatinib but not trastuzumab. Loss of PTEN or the presence of activating mutations in PI3K marked resistance to trastuzumab, but lapatinib response was independent of these factors. Thus, increased activation of the PI3K/AKT pathway correlates with resistance to trastuzumab, which can be overcome by lapatinib. In conclusion, pharmacologic targeting of the PI3K/AKT pathway may provide benefit to HER2-positive breast cancer patients who are resistant to trastuzumab therapy. Mol Cancer Ther; 9(6); 1489–502. ©2010 AACR.

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Supplementary Figure 3 from Tyrosine Phosphorylation Profiling Reveals the Signaling Network Characteristics of Basal Breast Cancer Cells

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Supplementary Table 5 from Tyrosine Phosphorylation Profiling Reveals the Signaling Network Characteristics of Basal Breast Cancer Cells

Supplementary Table 3 from Tyrosine Phosphorylation Profiling Reveals the Signaling Network Characteristics of Basal Breast Cancer Cells

Supplementary Figure 1 from Tyrosine Phosphorylation Profiling Reveals the Signaling Network Characteristics of Basal Breast Cancer Cells

Supplementary Figures PDF file - 1342K, Supplementary Figures for Croucher et al. Supplementary Figure 1: SILAC-based (phospho)-proteomic analysis in basal breast cancer cell lines following Lyn knockdown. Supplementary Figure 2: Lyn regulates a small fraction of the SFK signaling network in basal breast cancer cells. Supplementary Figure 3: Specificity of the SgK269 pY635 antibody. Supplementary Figure 4: Effect of Lyn knockdown on protein tyrosine phosphorylation. Supplementary Figure 5: Sub-cellular location of SgK269. Supplementary Figure 6: Knockdown of Src does not affect SgK269 Y635 phosphorylation. Supplementary Figure 7: Functional role of SgK269 in MDA-MB-231 cells.

Supplementary Figure Legends 1-3 from Tyrosine Phosphorylation Profiling Reveals the Signaling Network Characteristics of Basal Breast Cancer Cells

Suppl Material & Suppl. Table S1

Supplementary Figure 2 from Tyrosine Phosphorylation Profiling Reveals the Signaling Network Characteristics of Basal Breast Cancer Cells

Supplementary Table 4 from Tyrosine Phosphorylation Profiling Reveals the Signaling Network Characteristics of Basal Breast Cancer Cells

Intrinsic and acquired resistance to HER-targeting drugs occurs in a significant proportion of HER2-overexpressing breast cancers. Thus, there remains a need to identify predictive biomarkers that could improve patient selection and circumvent these types of drug resistance. Here, we report the identification of neuromedin U (NmU) as an extracellular biomarker in cells resistant to HER-targeted drugs. NmU overexpression occurred in cells with acquired or innate resistance to lapatinib, trastuzumab, neratinib, and afatinib, all of which displayed a similar trend upon short-term exposure, suggesting NmU induction may be an early response. An analysis of 3,489 cases of breast cancer showed NmU to be associated with poor patient outcome, particularly those with HER2-overexpressing tumors independent of established prognostic indicators. Ectopic overexpression of NmU in drug-sensitive cells conferred resistance to all HER-targeting drugs, whereas RNAi-mediated attenuation sensitized cells exhibiting acquired or innate drug resistance. Mechanistic investigations suggested that NmU acted through HSP27 as partner protein to stabilize HER2 protein levels. We also obtained evidence of functional NmU receptors on HER2-overexpressing cells, with the addition of exogenous NmU eliciting an elevation in HER2 and EGFR expression along with drug resistance. Finally, we found that NmU seemed to function in cell motility, invasion, and anoikis resistance. In vivo studies revealed that NmU attenuation impaired tumor growth and metastasis. Taken together, our results defined NmU as a candidate drug response biomarker for HER2-overexpressing cancers and as a candidate therapeutic target to limit metastatic progression and improve the efficacy of HER-targeted drugs. Cancer Res; 74(14); 3821–33. ©2014 AACR.

The authors sought to estimate the prevalence of past-12-month and lifetime cannabis use and cannabis use disorder among U.S. veterans; to describe demographic, substance use disorder, and psychiatric disorder correlates of nonmedical cannabis use and cannabis use disorder; and to explore differences in cannabis use and cannabis use disorder prevalence among veterans in states with and without medical marijuana laws.Participants were 3,119 respondents in the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III) who identified as U.S. veterans. Weighted prevalences were calculated. Logistic regression analyses tested associations of nonmedical cannabis use and cannabis use disorder with demographic and clinical correlates and examined whether prevalence differed by state legalization status.The prevalences of any past-12-month cannabis use and cannabis use disorder were 7.3% and 1.8%, respectively. Lifetime prevalences were 32.5% and 5.7%, respectively. Past-12-month and lifetime cannabis use disorder prevalence estimates among nonmedical cannabis users were 24.4% and 17.4%, respectively. Sociodemographic correlates of nonmedical cannabis use and use disorder included younger age, male gender, being unmarried, lower income, and residing in a state with medical marijuana laws. Nonmedical cannabis use and use disorder were associated with most psychiatric and substance use disorders examined.Among veterans, the odds of nonmedical cannabis use and use disorder were elevated among vulnerable subgroups, including those with lower income or psychiatric disorders and among survey participants residing in states with medical marijuana laws. The study findings highlight the need for clinical attention (e.g., screening, assessment) and ongoing monitoring among veterans in the context of increasing legalization of cannabis.