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1.
Health Psychol ; 43(6): 462-475, 2024 Jun.
Article En | MEDLINE | ID: mdl-38619489

OBJECTIVE: Sexual minority men experience disproportionately elevated rates of skin cancers, likely driven by excess ultraviolet radiation exposure-namely through tanning behaviors. However, limited integrated theoretical models exist to explain sexual minority men's elevated skin cancer risk. The aim of the current study is to further test and refine an integrated theory of skin cancer risk behaviors among sexual minority men by incorporating minority stress into the integrated health behavior model of tanning. METHOD: The study employed a parallel mixed methods design, with a Phase 1 qualitative stage (N = 30) and a Phase 2 quantitative stage (Model 1: N = 320; Model 2: N = 319). In both phases, participants were sexual minority men, equally stratified as those with versus without recent tanning exposure and were recruited from across the United States. RESULTS: Qualitative and quantitative data supported the overall integrated model, with some quantitative paths varying depending on the tanning behavior outcome. Overall, appearance-related motives to tan and beliefs that tanning regulates affect emerged as the most consistent proximal predictors. Minority stress significantly predicted holding more positive attitudes toward tanning as an effective affect regulation strategy. CONCLUSIONS: The results from this mixed methods study support the inclusion of minority stressors into the adapted integrative health behavior model of tanning. Replication within prospective designs would strengthen the evidence for this model, which may be helpful in guiding future skin cancer prevention programs tailored to sexual minority men. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Sexual and Gender Minorities , Skin Neoplasms , Sunbathing , Humans , Male , Sexual and Gender Minorities/psychology , Skin Neoplasms/prevention & control , Adult , Sunbathing/psychology , Young Adult , Middle Aged , United States , Stress, Psychological/psychology , Risk-Taking , Adolescent
2.
Article En | MEDLINE | ID: mdl-38347114

BACKGROUND: CALGB 90401 (Alliance) was a phase III trial of 1050 patients with metastatic castration-resistant prostate cancer (mCRPC) comparing docetaxel, prednisone, bevacizumab (DP+B) versus DP alone. While this trial did not show an improvement in overall survival (OS), there were improved intermediate outcomes suggesting that subsets of men may derive benefit from this combination. The purpose of this analysis was to identify prognostic and predictive biomarkers associated with OS and progression-free survival (PFS) benefit from DP+B. METHODS: Baseline EDTA plasma samples from 650 consenting patients were analyzed for 24 biomarkers. The proportional hazards model was utilized to test for the prognostic and predictive importance of the biomarkers for OS. The statistically significant biomarkers of OS were further investigated for prognostic and predictive importance for other secondary outcomes. RESULTS: 15 markers [ICAM-1, VEGF-R3, TIMP-1, TSP-2, Ang-2, Her-3, Osteopontin (OPN), PlGF, VCAM-1, HGF, VEGF, Chromogranin A, IL-6, VEGF-R1, BMP-9] were prognostic of OS, while 9 markers (ICAM-1, VEGF-R3, Her-3, TIMP-1, Ang-2, OPN, PlGF, HGF, and VEGF) were also prognostic of PFS. All markers were statistically significant in univariate analyses after adjustment for multiplicity (FDR < 0.1). In multivariable analyses of OS adjusting for risk score, seven markers had FDR < 0.1, including ICAM-1, VEGF-R3, TIMP-1, Ang-2, VEGF, TSP-2 and HGF. In unadjusted analysis, OPN was predictive of PFS improvement with DP+B, in both univariate and multivariable analysis. However, none of the biomarkers tested were predictive of clinical outcomes after adjusting for multiple comparisons. CONCLUSIONS: Multiple biomarkers were identified in CALGB 90401 as prognostic of clinical outcomes but not predictive of OS. While OPN may have promise as a potential biomarker for anti-angiogenic therapies, further mechanistic and clinical studies are needed to determine the underlying biology and potential clinical application.

3.
Anal Chem ; 96(4): 1419-1426, 2024 Jan 30.
Article En | MEDLINE | ID: mdl-38240047

Resolution and sensitivity improvements in mass spectrometry technology have enabled renewed attempts at solving challenging analytical issues. One such issue involves the analysis of energetic ionic species. Energetic ionic species make up an important class of chemical materials, and a more robust and versatile analytical platform would provide tremendous value to the analytical community. Initial attempts at quantification of energetic ionic species employed high-resolution time-of-flight measurements with crown ether (CE) complexation and flow injection analysis (FIA). In this investigation, ammonium nitrate (AN) and urea nitrate (UN) in the presence of a crown ether complexation agent were explored by using high-resolution orbitrap mass spectrometry. Product ion scans of these signature complexes reveal positive identification of these energetic ionic species. Finally, quantification was demonstrated for both flow injection and liquid chromatography-mass spectrometry (LC-MS) analysis, suggesting the capability for routine and rapid analysis of these energetic ionic materials.

4.
Sci Adv ; 10(1): eadj1741, 2024 Jan 05.
Article En | MEDLINE | ID: mdl-38170782

Bacteria can swim upstream in a narrow tube and pose a clinical threat of urinary tract infection to patients implanted with catheters. Coatings and structured surfaces have been proposed to repel bacteria, but no such approach thoroughly addresses the contamination problem in catheters. Here, on the basis of the physical mechanism of upstream swimming, we propose a novel geometric design, optimized by an artificial intelligence model. Using Escherichia coli, we demonstrate the anti-infection mechanism in microfluidic experiments and evaluate the effectiveness of the design in three-dimensionally printed prototype catheters under clinical flow rates. Our catheter design shows that one to two orders of magnitude improved suppression of bacterial contamination at the upstream end, potentially prolonging the in-dwelling time for catheter use and reducing the overall risk of catheter-associated urinary tract infection.


Urinary Catheters , Urinary Tract Infections , Humans , Urinary Catheters/microbiology , Artificial Intelligence , Urinary Tract Infections/prevention & control , Urinary Tract Infections/microbiology , Bacteria , Escherichia coli , Hydrolases
5.
AIDS Behav ; 28(3): 759-773, 2024 Mar.
Article En | MEDLINE | ID: mdl-37773474

Latinx men who have sex with men (MSM) are an at-risk population for new HIV diagnoses. Pre-exposure prophylaxis (PrEP) is a suite of biomedical approaches to prevent HIV infection. Latinx MSM are less likely to take PrEP compared to non-Latinx White MSM. This qualitative study identified interpersonal- and community-level barriers and facilitators of PrEP among young adult Latinx MSM. Using stratified purposeful sampling, 27 Latinx men, ages 19-29 years and living in a US-Mexico border region, completed self-report demographic surveys and participated in semi-structured in-depth interviews assessing barriers and facilitators to PrEP. Directed content analysis was used to identify both a priori and emerging themes. Most participants reported that other people, including peers, friends, partners, and health care providers were both supportive and discouraging of PrEP use. Participants' intersectional identities as members of both Latinx and LGBTQ+ (Lesbian, Gay, Bisexual, Transgender, Queer) communities both hindered and facilitated PrEP use.


Anti-HIV Agents , HIV Infections , Pre-Exposure Prophylaxis , Sexual and Gender Minorities , Humans , Male , Young Adult , Anti-HIV Agents/therapeutic use , Hispanic or Latino , HIV Infections/epidemiology , HIV Infections/prevention & control , HIV Infections/drug therapy , Homosexuality, Male , Mexico/epidemiology , Qualitative Research , United States , Adult
6.
Int J Biol Macromol ; 253(Pt 6): 127294, 2023 Dec 31.
Article En | MEDLINE | ID: mdl-37813217

Bacteria form very often biofilms where they embed in a self-synthesized matrix exhibiting a gel-like appearance. Matrices offer several advantages, including defence against external threats and the easiness of intercellular communication. In infections, biofilm formation enhances bacteria resistance against antimicrobials, causing serious clinical problems for patients' treatments. Biofilm matrices are composed of proteins, extracellular DNA, and polysaccharides, the latter being the major responsible for matrix architecture. The repeating unit of the biofilm polysaccharide synthesized by Burkholderia multivorans strain C1576 contains two mannoses and two sequentially linked rhamnoses, one of them 50 % methylated on C-3. Rhamnose, a 6-deoxysugar, has lower polarity than other common monosaccharides and its methylation further reduces polarity. This suggests a possible role of this polysaccharide in the biofilm matrix; in fact, computer modelling and atomic force microscopy studies evidenced intra- and inter-molecular non-polar interactions both within polysaccharides and with aliphatic molecules. In this paper, the polysaccharide three-dimensional morphology was investigated using atomic force microscopy in both solid and solution states. Independent evidence of the polymer conformation was obtained by transmission electron microscopy which confirmed the formation of globular compact structures. Finally, data from computer dynamic simulations were used to model the three-dimensional structure.


Burkholderia , Polysaccharides, Bacterial , Humans , Polysaccharides, Bacterial/chemistry , Burkholderia/metabolism , Biofilms , Microscopy, Atomic Force
7.
Proc Natl Acad Sci U S A ; 120(18): e2219900120, 2023 May 02.
Article En | MEDLINE | ID: mdl-37094152

Nonequilibrium phase transitions are routinely observed in both natural and synthetic systems. The ubiquity of these transitions highlights the conspicuous absence of a general theory of phase coexistence that is broadly applicable to both nonequilibrium and equilibrium systems. Here, we present a general mechanical theory for phase separation rooted in ideas explored nearly a half-century ago in the study of inhomogeneous fluids. The core idea is that the mechanical forces within the interface separating two coexisting phases uniquely determine coexistence criteria, regardless of whether a system is in equilibrium or not. We demonstrate the power and utility of this theory by applying it to active Brownian particles, predicting a quantitative phase diagram for motility-induced phase separation in both two and three dimensions. This formulation additionally allows for the prediction of novel interfacial phenomena, such as an increasing interface width while moving deeper into the two-phase region, a uniquely nonequilibrium effect confirmed by computer simulations. The self-consistent determination of bulk phase behavior and interfacial phenomena offered by this mechanical perspective provide a concrete path forward toward a general theory for nonequilibrium phase transitions.

8.
Soft Matter ; 19(7): 1384-1392, 2023 Feb 15.
Article En | MEDLINE | ID: mdl-36723138

We analyze a dilute suspension of active particles confined between walls and subjected to fields that can modulate particle speed as well as orientation. Generally, the particle distribution is different in the bulk compared to near the walls. In the bulk, particles tend to accumulate in the regions of low speed, but in the presence of an orienting field normal to the walls, particles rotate to align with the field and accumulate in the field direction. At the walls, particles tend to accumulate pointing into the walls and thereby exert pressure on walls. But the presence of strong orienting fields can cause the particles to reorient away from the walls, and hence shows a possible mechanism for preventing contamination of surfaces. The pressure at the walls depends on the wall separation and the field strengths. This work demonstrates how multiple fields with different functionalities can be used to control active matter under confinement.

9.
J Chem Phys ; 158(7): 074904, 2023 Feb 21.
Article En | MEDLINE | ID: mdl-36813709

In striking contrast to equilibrium systems, inertia can profoundly alter the structure of active systems. Here, we demonstrate that driven systems can exhibit effective equilibrium-like states with increasing particle inertia, despite rigorously violating the fluctuation-dissipation theorem. Increasing inertia progressively eliminates motility-induced phase separation and restores equilibrium crystallization for active Brownian spheres. This effect appears to be general for a wide class of active systems, including those driven by deterministic time-dependent external fields, whose nonequilibrium patterns ultimately disappear with increasing inertia. The path to this effective equilibrium limit can be complex, with finite inertia sometimes acting to accentuate nonequilibrium transitions. The restoration of near equilibrium statistics can be understood through the conversion of active momentum sources to passive-like stresses. Unlike truly equilibrium systems, the effective temperature is now density dependent, the only remnant of the nonequilibrium dynamics. This density-dependent temperature can in principle introduce departures from equilibrium expectations, particularly in response to strong gradients. Our results provide additional insight into the effective temperature ansatz while revealing a mechanism to tune nonequilibrium phase transitions.

10.
Carbohydr Res ; 524: 108741, 2023 Feb.
Article En | MEDLINE | ID: mdl-36716692

Potential of Mean Force Ramachandran energy maps in aqueous solution have been prepared for all of the glycosidic linkages found in the C1576 exopolysaccharide from the biofilms of the bacterial species Burkholderia multivorans, a member of the Burkholderia cepacian complex that was isolated from a cystic fibrosis patient. C1576 is a rhamnomannan with a tetrasaccharide repeat unit. In general, for the four linkage types in this polymer, hydration did not produce dramatic changes in the Ramachandran energy surfaces, with the 3-methyl-α-d-rhamnopyranose-(1→3)-α-d-rhamnopyranose case exhibiting the greatest hydration change, with the global minimum energy conformation shifting by more than 80° in ψ. However, hydration did reduce the rigidity of all the linkages, increasing the overall flexibility of this polysaccharide.


Burkholderia , Disaccharides , Humans , Molecular Conformation , Biofilms
11.
PLoS One ; 17(12): e0279618, 2022.
Article En | MEDLINE | ID: mdl-36584170

BACKGROUND: Elevated levels of suicidality, ADHD, mental ill-health and substance disorders are reported among college students globally, yet few receive treatment. Some faculties and courses appear to have more at-risk students than others. The current study aimed to determine if students commencing college in different academic disciplines were at a heightened risk for psychopathology, substance use disorders and suicidal behaviour, and examined variations in help-seeking behaviour. MATERIALS AND METHODS: The study utilised data collected from 1,829 first-year undergraduate students as part of the Student Psychological Intervention Trial (SPIT) which commenced in September 2019 across four Ulster University campuses in Northern Ireland and an Institute of Technology, in the North-West of Ireland. The SPIT study is part of the World Mental Health International College Student Initiative (WMH-ICS) which uses the WMH-CIDI to identify 12-month and lifetime disorders. RESULTS: Students from Life and Health Sciences reported the lowest rates of a range of psychological problems in the year prior to commencing college, while participants studying Arts and Humanities displayed the highest levels (e.g. depression 20.6%; social anxiety 38.8%). However, within faculty variations were found. For example, psychology students reported high rates, while nursing students reported low rates. Variations in help seeking behaviour were also revealed, with male students less likely to seek help. CONCLUSIONS: Detecting specific cohorts at risk of psychological disorders and suicidality is challenging. This study revealed that some academic disciplines have more vulnerable students than others, with many reluctant to seek help for their problems. It is important for educators to be aware of such issues and for colleges to provide information and support to students at risk. Tailored interventions and prevention strategies may be beneficial to address the needs of students from different disciplines.


Help-Seeking Behavior , Mental Disorders , Suicide , Humans , Male , Suicidal Ideation , Mental Disorders/epidemiology , Mental Disorders/therapy , Mental Disorders/psychology , Students/psychology , Universities
12.
BMJ Open ; 12(12): e061695, 2022 12 22.
Article En | MEDLINE | ID: mdl-36549725

INTRODUCTION: Past research has shown that construction industry workers are at an elevated risk of suicide, however, to date, no study has examined in detail the characteristics of individuals who work in the construction industry and experience distress. This research aims to understand the characteristics, including sociodemographic characteristics, health services utilisation and contacts with non-clinical services, of individuals working within the construction industry and who experience distress, and to quantify the costs and benefits of different help-seeking pathways. METHODS AND ANALYSIS: This study is a data linkage study, based on routinely collected administrative data from construction industry organisations and Queensland Health (QH). Expected outcomes include prevalence of distress, articulated to non-clinical construction industry agencies, descriptive findings on characteristics and help-seeking pathways and health economic analysis. Individuals who experienced distress but who did not contact any of the participating construction industry organisations will not be part of this research. ETHICS AND DISSEMINATION: This data linkage study was approved by Human Research Ethics Committee of The University of Queensland (2021/HE001885). Findings will be presented descriptively to describe the cohort as a whole and stratified by key demographic characteristics, and to provide estimates of prevalence of distress, including timing, frequency and type of contacts. In addition, health economic analysis will be undertaken. Dissemination of findings will be undertaken following consultation of all project investigators, construction industry organisations and peer-led interest groups and lived-experience organisations to ensure translation merit of all findings. Results will be published as peer-reviewed journal articles and publicly available reports.


Construction Industry , Suicide , Humans , Costs and Cost Analysis , Prevalence , Information Storage and Retrieval
13.
ACS Nano ; 16(10): 16191-16200, 2022 Oct 25.
Article En | MEDLINE | ID: mdl-36227266

Control of self-propelled particles is central to the development of many microrobotic technologies, from dynamically reconfigurable materials to advanced lab-on-a-chip systems. However, there are few physical principles by which particle trajectories can be specified and can be used to generate a wide range of behaviors. Within the field of ray optics, a single principle for controlling the trajectory of light─Snell's law─yields an intuitive framework for engineering a broad range of devices, from microscopes to cameras and telescopes. Here we show that the motion of self-propelled particles gliding across a resistance discontinuity is governed by a variant of Snell's law, and develop a corresponding ray optics for gliders. Just as the ratio of refractive indexes sets the path of a light ray, the ratio of resistance coefficients is shown to determine the trajectories of gliders. The magnitude of refraction depends on the glider's shape, in particular its aspect ratio, which serves as an analogue to the wavelength of light. This enables the demixing of a polymorphic, many-shaped, beam of gliders into distinct monomorphic, single-shaped, beams through a friction prism. In turn, beams of monomorphic gliders can be focused by spherical and gradient friction lenses. Alternatively, the critical angle for total internal reflection can be used to create shape-selective glider traps. Overall our work suggests that furthering the analogy between light and microscopic gliders may be used for sorting, concentrating, and analyzing self-propelled particles.

14.
J Chem Phys ; 157(10): 104119, 2022 Sep 14.
Article En | MEDLINE | ID: mdl-36109215

In microrheology, the local rheological properties, such as the viscoelasticity of a complex fluid, are inferred from the free or forced motion of embedded colloidal probe particles. Theoretical machinery developed for forced-probe microrheology of colloidal suspensions focused on either constant-force (CF) or constant-velocity (CV) probes, while in experiments, neither the force nor the kinematics of the probe is fixed. More importantly, the constraint of CF or CV introduces a difficulty in the meaningful quantification of the fluctuations of the probe due to a thermodynamic uncertainty relation. It is known that, for a Brownian particle trapped in a harmonic potential well, the product of the standard deviations of the trap force and the particle position is dkBT in d dimensions, with kBT being the thermal energy. As a result, if the force (position) is not allowed to fluctuate, the position (force) fluctuation becomes infinite. To allow the measurement of fluctuations in theoretical studies, in this work, we consider a microrheology model in which the embedded probe is dragged along by a moving harmonic potential so that both its position and the trap force are allowed to fluctuate. Starting from the full Smoluchowski equation governing the dynamics of N hard active Brownian particles, we derive a pair Smoluchowski equation describing the dynamics of the probe as it interacts with one bath particle by neglecting hydrodynamic interactions among particles in the dilute limit. From this, we determine the mean and the variance (i.e., fluctuation) of the probe position in terms of the pair probability distribution. We then characterize the behavior of the system in the limits of both weak and strong trap. By taking appropriate limits, we show that our generalized model can be reduced to the well-studied CF or CV microrheology models.

15.
Arch Sex Behav ; 51(5): 2523-2533, 2022 07.
Article En | MEDLINE | ID: mdl-35705769

Sexual minority men (SMM) remain disproportionately burdened by sexually transmitted infections. Although gay community involvement has been theorized to be protective against many negative health outcomes, research examining the association between community involvement and condomless anal sex (CAS) has yielded conflicting results. The current study, conducted between 2018-2020, examined whether the importance one places on various aspects of community involvement was associated with CAS among a sample of young adult SMM aged 18-34 years with body image concerns (N = 180). Gay community involvement was measured using the Importance of Gay Community Scale, and the results of an exploratory factor analysis indicated the presence of two factors: "social activism" and "going out/nightlife." A zero-inflated Poisson regression was conducted to examine the association between gay "social activism," "going out/nightlife," and their interaction with the number of CAS partners. Upon examining a significant interaction, "social activism" had a protective effect against CAS at low levels of "going out/nightlife," but this effect was non-significant at higher levels. These results suggest that encouraging gay community involvement through activism could be effective at reducing CAS and addressing the health disparity that exists within this population.


HIV Infections , Sexual and Gender Minorities , Community Participation , HIV Infections/epidemiology , Homosexuality, Male , Humans , Male , Sexual Behavior , Sexual Partners , Unsafe Sex , Young Adult
16.
Body Image ; 41: 109-127, 2022 Jun.
Article En | MEDLINE | ID: mdl-35247866

Body image is a critical component of an individual's sexual experiences. This makes it critical to identify demographic and sociocultural correlates of sexuality-related body image: the subjective feelings, cognitions, and evaluations related to one's body in the context of sexual experience. We examined how sexuality-related body image differed by gender, sexual orientation, race, age, and BMI. Four items assessing sexuality-related body image were completed by 11,620 U.S. adults: self-perceived sex appeal of their body, nude appearance satisfaction, and the extent to which they believed that body image positively or negatively affected their sexual enjoyment and feelings of sexual acceptability as a partner. Men reported slightly less nude appearance dissatisfaction and fewer negative effects of body image on sexual enjoyment and sexual acceptability than women, but did not differ in reported sex appeal. Poorer sexuality-related body image was reported by people with higher BMIs, not in relationships, who had sex less frequently, among White compared to Black women and men, and among gay compared to heterosexual men. Data also revealed a subgroup of respondents who reported that their body image had a positive impact on their sex lives. The findings highlight a need for interventions addressing sexuality-related body image.


Body Image , Sexuality , Adult , Body Image/psychology , Demography , Female , Heterosexuality , Humans , Male , Personal Satisfaction , Sexual Behavior
17.
Soft Matter ; 18(14): 2757-2766, 2022 Apr 06.
Article En | MEDLINE | ID: mdl-35315471

Passive Brownian particles partition homogeneously between a porous medium and an adjacent fluid reservoir. In contrast, active particles accumulate near boundaries and can therefore preferentially partition into the porous medium. Understanding how active particles interact with and partition into such an environment is important for optimizing particle transport. In this work, both the initial transient and steady behavior as active swimmers partition into a porous medium from a bulk fluid reservoir are investigated. At short times, the particle number density in the porous medium exhibits an oscillatory behavior due to the particles' ballistic motion when time t < τR, where τR is the reorientation time of the active particles. At longer times, t > L2/Dswim, the particles diffuse from the reservoir into the porous medium, leading to a steady state concentration partitioning. Here, L is the characteristic length scale of the porous medium and Dswim = U0/d(d - 1), where U0 is the intrinsic swim speed of the particles,  = U0τR is the particles' run, or persistence, length, and d is the dimension of the reorientation process. An analytical prediction is developed for this partitioning for spherical obstacles connected to a fluid reservoir in both two and three dimensions based on the Smoluchowski equation and a macroscopic mechanical momentum balance. The analytical prediction agrees well with Brownian dynamics simulations.

18.
J Atten Disord ; 26(11): 1437-1451, 2022 09.
Article En | MEDLINE | ID: mdl-35118906

OBJECTIVE: To evaluate the prevalence of suicidal ideation (SI), plans and attempts, and non-suicidal self-injury (NSSI) among students with attention deficit hyperactivity disorder (ADHD). Furthermore, we explored the mediating effects of depression, anxiety, alcohol and substance use on the association between ADHD and suicidal behaviors and NSSI. METHOD: Participants were first-year undergraduate students (n = 1,829) recruited as part of the World Mental Health International College Student Initiative. Participants completed validated clinical measures online. RESULTS: The prevalence of suicide behaviors and NSSI were significantly higher among students with ADHD than those without. Mediation analyses indicated that ADHD directly and indirectly increased suicidal behaviors and NSSI. While ADHD increased suicidal behaviors and NSSI through depression, ADHD and the co-variates age and gender also had indirect effects on suicidal behaviors via substance use. CONCLUSIONS: Specific predictors of risk were identified for students with ADHD which may inform the development of more targeted mental health and suicide prevention strategies across campuses.


Attention Deficit Disorder with Hyperactivity , Substance-Related Disorders , Attention Deficit Disorder with Hyperactivity/epidemiology , Attention Deficit Disorder with Hyperactivity/psychology , Humans , Mental Health , Risk Factors , Students/psychology , Substance-Related Disorders/epidemiology , Suicidal Ideation
19.
Cancer Chemother Pharmacol ; 89(3): 413-422, 2022 Mar.
Article En | MEDLINE | ID: mdl-35171350

PURPOSE: Acquired resistance to EGFR inhibitors in metastatic colorectal cancer (mCRC) remains a hurdle for effective treatment. MET amplification has been indicated as a driver of acquired resistance. Clinical activity has been demonstrated for the combination of EGFR and MET inhibitors in mCRC. But the impact of this regimen on angiogenesis and inflammation remains largely unknown. METHODS: In this non-randomized, open-label phase Ib/II study, four patients were treated with cabozantinib alone and 25 patients received the combination of cabozantinib and panitumumab. MET amplification was detected in blood in all four patients treated with cabozantinib monotherapy and 5/25 patients treated with cabozantinib and panitumumab combination therapy. Plasma samples from 28 patients were available for biomarker analysis. RESULTS: A panel of circulating protein biomarkers was assessed in patient plasma at baseline and on-treatment. Baseline marker levels were analyzed for prognostic value for clinical outcomes, including MET amplification as a covariate. HGF and OPN were prognostic for both progression-free survival (PFS) and overall survival (OS), while six markers (IL-6, VCAM-1, VEGF-R1, TSP-2, TIMP-1, ICAM-1) were prognostic only for OS. In patients with MET amplification, baseline PDGF-AA, PDGF-BB, TGF-ß1, and VEGF-C levels were significantly higher, whereas baseline TGFß-R3 levels were significantly lower than MET non-amplified patients. On-treatment change of four markers (CD73, PlGF, PDGF-BB, VEGF) were significantly different between MET amplified and non-amplified subpopulations. CONCLUSION: This study identified circulating HGF and several inflammatory and angiogenic proteins as prognostic biomarkers. Furthermore, MET amplification status is associated with both baseline expression and on-treatment modulation of members of angiogenesis and TGF-ß pathway proteins. CLINICAL TRIALS REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT02008383.


Colonic Neoplasms , Colorectal Neoplasms , Rectal Neoplasms , Anilides , Becaplermin/therapeutic use , Biomarkers , Colonic Neoplasms/drug therapy , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , ErbB Receptors , Humans , Panitumumab/therapeutic use , Pyridines , Rectal Neoplasms/drug therapy , Vascular Endothelial Growth Factor A
20.
Psychiatry Res ; 307: 114314, 2022 01.
Article En | MEDLINE | ID: mdl-34864232

The increase in psychological disorders and suicidal behaviour in students is a reason for growing concern. Some may start university with pre-existing problems, while others develop problems during this time. It is important to evaluate mental health and wellbeing early, identifying those at risk. The aim of this study was to compare mental health problems and help-seeking behaviour between students in Northern Ireland (NI) and the Republic of Ireland (ROI). Whilst geographically proximate, the institutions span a cross-border region with distinct education and healthcare systems. First-year undergraduate students (n = 1828) were recruited in September 2019 as part of the World Mental Health International College Student Initiative. Suicidal behaviour, mental health and substance disorders were investigated using the World Mental Health- Composite International Diagnostic Interview. Prevalence of disorders was high, with more ROI students experiencing problems than NI students. Students were significantly more likely to experience mental health problems if they were female (p<0.001), non-heterosexual (p<0.0001), and over the age of 21 (p<0.0001). These findings show that many students are starting university with high levels of psychopathology and suicidal behaviour, highlighting the importance of early intervention which may need to be tailored to different student populations.


Mental Disorders , Suicidal Ideation , Female , Humans , Mental Disorders/epidemiology , Mental Disorders/psychology , Mental Health , Students/psychology , Universities
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