Environment and Local Substrate Availability Effects on Harem Formation in a Polygynous Bark Beetle.

Many forms of polygyny are observed across different animal groups. In some species, groups of females may remain with a single male for breeding, often referred to as "harem polygyny". The environment and the amount of habitat available for feeding, mating and oviposition may have an effect on the formation of harems. We aimed to determine how the surrounding environment (a harvested or unharvested pine plantation) and availability of local substrate affect the harems of the bark beetle, Ips grandicollis (Coleoptera: Curculionidae: Scolytinae). In a harvested pine plantation with large amounts of available habitat, the population density of these beetles is much higher than in unharvested plantations. We found the number of females per male to be significantly greater in the harvested plantation than the unharvested one. Additionally, the amount of substrate available in the immediate local vicinity (the number of logs in replicate piles) also influences the number of beetles attracted to a log and size of individual harems. We also examined how females were distributing themselves in their galleries around the males' nuptial chamber, as previous work has demonstrated the potential for competition between neighbouring females and their offspring. Females do not perform clumping, suggesting some avoidance when females make their galleries, but they also do not distribute themselves evenly. Female distribution around the male's nuptial chamber appears to be random, and not influenced by other females or external conditions.

The Disparity Between Public Utilization and Surgeon Awareness of the STS Patient Education Website.

BACKGROUND: Many online resources currently provide healthcare information to the public. In 2015, the Society of Thoracic Surgeons (STS) created a multimedia web portal (ctsurgerypatients.org) to educate the public regarding cardiothoracic surgery and provide an informative tool to which cardiothoracic surgeons could refer patients. METHODS: A patient education task force was created, and disease-specific content was created for 25 pathological conditions. After launching the website online, a marketing campaign was initiated to make STS members aware of its availability. Website visits were monitored, and an online survey for public users was created. An email survey was sent to STS members to evaluate awareness and content. Surveys were analyzed for effectiveness and utilization by both public users and STS member surgeons. RESULTS: From 2016 to 2018, the website had more than 1 million visits, with visits increasing yearly. Surveyed user ratings of the website were positive regarding quality and utility of the information provided. STS member response was poor (379 responses of 6347 emails), and 78.3% of responders were unaware of the website. Surgeon responders were positive about the content, though many still refrain from referring patients. CONCLUSIONS: Online education for cardiothoracic surgery is seeing increased public use, with high ratings for content and utility. Despite aggressive marketing to STS members, most remain unaware of this website's existence. Those who are aware approve of its content, but adoption of referring patients to it has been slow. Improved strategies are necessary to make surgeons aware of this STS-provided service and increase patient referrals to it.

Phase I Study of Veliparib (ABT-888) Combined with Cisplatin and Vinorelbine in Advanced Triple-Negative Breast Cancer and/or BRCA Mutation-Associated Breast Cancer.

PURPOSE: Cisplatin is synergistic with vinorelbine and the PARP inhibitor veliparib, and has antineoplastic activity in triple-negative breast cancer (TNBC) and BRCA mutation-associated breast cancer. This phase I study assessed veliparib with cisplatin and vinorelbine. EXPERIMENTAL DESIGN: A 3+3 dose-escalation design evaluated veliparib administered twice daily for 14 days with cisplatin (75 mg/m(2) day 1) and vinorelbine (25 mg/m(2) days 1, 8) every 21 days, for 6 to 10 cycles, followed by veliparib monotherapy. Pharmacokinetics, measurement of poly(ADP-ribose) in peripheral blood mononuclear cells, and preliminary efficacy were assessed. IHC and gene-expression profiling were evaluated as potential predictors of response. RESULTS: Forty-five patients enrolled in nine dose cohorts plus five in an expansion cohort at the highest dose level and recommended phase II dose, 300 mg twice daily. The MTD of veliparib was not reached. Neutropenia (36%), anemia (30%), and thrombocytopenia (12%) were the most common grade 3/4 adverse events. Best overall response for 48 patients was radiologic response with 9-week confirmation for 17 (35%; 2 complete, 15 partial), and stable disease for 21 (44%). Germline BRCA mutation presence versus absence was associated with 6-month progression-free survival [PFS; 10 of 14 (71%) vs. 8 of 27 (30%), mid-P = 0.01]. Median PFS for all 50 patients was 5.5 months (95% confidence interval, 4.1-6.7). CONCLUSIONS: Veliparib at 300 mg twice daily combined with cisplatin and vinorelbine is well tolerated with encouraging response rates. A phase II randomized trial is planned to assess veliparib's contribution to cisplatin chemotherapy in metastatic TNBC and BRCA mutation-associated breast cancer. Clin Cancer Res; 22(12); 2855-64. ©2016 AACR.

ReCAP: Comparison of Independent Error Checks for Oral Versus Intravenous Chemotherapy.

PURPOSE: Intravenous (IV) chemotherapy is routinely delivered to patients in hospital settings, where safeguards such as independent checks and guidelines govern their administration. In contrast, oral chemotherapy, which is typically ordered in a cancer center but dispensed and administered in the community and home, respectively, is subject to fewer controls. Research in the United States has found that few safeguards in routine use for IV chemotherapy have been adopted for oral chemotherapy; however, less is known about the Canadian context. The objective of this study was to determine whether similar safeguards, in the form of independent checks, existed to identify potential errors related to both formulations. METHODS: Human factors specialists conducted observations and interviews in cancer center clinics, a cancer center pharmacy, and four community pharmacies across Nova Scotia. Processes were analyzed to determine if an independent check was performed, which qualified provider completed the check, and at what point of the process the check occurred. RESULTS: A total of 57 systematic checks were identified for IV chemotherapy, whereas only six systematic checks were identified for oral chemotherapy. Community pharmacists were the only qualified professionals involved in independent systematic checking of oral chemotherapy, which occurred during ordering and dispensing. CONCLUSION: There is an enormous opportunity for pharmacists and other qualified professionals to take on an expanded role in improving patient safety for oral chemotherapy. Greater involvement of pharmacists, in both the clinic environment and the community, would facilitate increased systematic checking, which could improve patient safety related to oral chemotherapy.

Seniors managing multiple medications: using mixed methods to view the home care safety lens.

BACKGROUND: Patient safety is a national and international priority with medication safety earmarked as both a prevalent and high-risk area of concern. To date, medication safety research has focused overwhelmingly on institutional based care provided by paid healthcare professionals, which often has little applicability to the home care setting. This critical gap in our current understanding of medication safety in the home care sector is particularly evident with the elderly who often manage more than one chronic illness and a complex palette of medications, along with other care needs. This study addresses the medication management issues faced by seniors with chronic illnesses, their family, caregivers, and paid providers within Canadian publicly funded home care programs in Alberta (AB), Ontario (ON), Quebec (QC) and Nova Scotia (NS). METHODS: Informed by a socio-ecological perspective, this study utilized Interpretive Description (ID) methodology and participatory photographic methods to capture and analyze a range of visual and textual data. Three successive phases of data collection and analysis were conducted in a concurrent, iterative fashion in eight urban and/or rural households in each province. A total of 94 participants (i.e., seniors receiving home care services, their family/caregivers, and paid providers) were interviewed individually. In addition, 69 providers took part in focus groups. Analysis was iterative and concurrent with data collection in that each interview was compared with subsequent interviews for converging as well as diverging patterns. RESULTS: Six patterns were identified that provide a rich portrayal of the complexity of medication management safety in home care: vulnerabilities that impact the safe management and storage of medication, sustaining adequate supports, degrees of shared accountability for care, systems of variable effectiveness, poly-literacy required to navigate the system, and systemic challenges to maintaining medication safety in the home. CONCLUSIONS: There is a need for policy makers, health system leaders, care providers, researchers, and educators to work with home care clients and caregivers on three key messages for improvement: adapt care delivery models to the home care landscape; develop a palette of user-centered tools to support medication safety in the home; and strengthen health systems integration.

Coping, PTSD symptoms, and alcohol involvement in trauma-exposed college students in the first three years of college.

The objective of the present study was to examine prospective, bidirectional associations among posttraumatic stress disorder (PTSD) symptoms, coping style, and alcohol involvement (use, consequences) in a sample of trauma-exposed students just entering college. We also sought to test the mechanistic role that coping may play in associations between PTSD symptoms and problem alcohol involvement over time. Participants (N = 734) completed measures of trauma exposure, PTSD symptoms, coping, and alcohol use and consequences in September of their first college year and again each September for the next 2 years. We observed reciprocal associations between PTSD and negative coping strategies. In our examination of a mediated pathway through coping, we found an indirect association from alcohol consequences and PTSD symptoms via negative coping, suggesting that alcohol consequences may exacerbate posttraumatic stress over time by promoting negative coping strategies. Trauma characteristics such as type (interpersonal vs. noninterpersonal) and trauma reexposure did not moderate these pathways. Models were also invariant across gender. Findings from the present study point to risk that is conferred by both PTSD and alcohol consequences for using negative coping approaches, and through this, for posttraumatic stress. Interventions designed to decrease negative coping may help to offset this risk, leading to more positive outcomes for those students who enter college with trauma exposure.

Posttraumatic stress symptoms and alcohol problems: self-medication or trait vulnerability?

BACKGROUND AND OBJECTIVES: Posttraumatic stress symptoms (PTSD) and problem alcohol use (ALC) commonly co-occur, but the nature of this co-occurrence is unclear. Self-medication explanations have been forwarded, yet traits such as tendency toward negative emotionality and behavioral disconstraint also have been implicated. In this study we test three competing models (Self-Medication, Trait Vulnerability, Combined Dual Pathway) of PTSD-ALC prospectively in a college sample. METHOD: Participants (N=659; 73% female, M age=18) provided data at college matriculation (Time 1) and 1 year later (Time 2). RESULTS: Structural equation models showed disconstraint to meditate the path from PTSD symptoms to alcohol problems, supporting a trait vulnerability conceptualization. Findings regarding negative emotionality and self-medication were more mixed. Negative emotionality played a stronger role in cross-sectional than in prospective analyses, suggesting the importance of temporal proximity. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Self-regulation skills may be an important focus for clinicians treating PTSD symptoms and alcohol misuse disorders concurrently.

Phase 1b study of otlertuzumab (TRU-016), an anti-CD37 monospecific ADAPTIR™ therapeutic protein, in combination with rituximab and bendamustine in relapsed indolent lymphoma patients.

PURPOSE: CD37 is cell surface tetraspanin present on normal and malignant B cells. Otlertuzumab (TRU-016) is a novel humanized anti-CD37 protein therapeutic that triggers direct caspase independent apoptosis of malignant B cells and induces antibody-dependent cell-mediated cytotoxicity. This study evaluated the safety, pharmacokinetics, and efficacy of otlertuzumab administered in combination with rituximab and bendamustine to patients with relapsed, indolent B-cell non-Hodgkin Lymphoma (NHL). METHODS: Patients with relapsed or refractory NHL received otlertuzumab (10 or 20 mg/kg) intravenously (IV) on days 1 and 15, bendamustine (90 mg/m(2)) on days 1 and 2, and rituximab (375 mg/m(2)) on day 1 for up to six 28 day cycles. Responses were determined using standard criteria. RESULTS: Twelve patients were treated with 6 patients at each dose level; median age was 57 years (range, 51-79), and median number of prior regimens was 3 (range, 1-4). All patients had relapsed after prior rituximab including 7 refractory to their most recent previous treatment. In the 10 and 20 mg/kg dose cohorts, the mean half-life was 8 and 10 days following the first dose, and 12 or 14 days following 12 doses of otlertuzumab, respectively. Overall response rate was 83% (10/12) with 4 CRs (32%). The most frequent adverse events were neutropenia, nausea, fatigue, leukopenia, and insomnia; most were grade 1 or 2. CONCLUSIONS: Otlertuzumab in combination with rituximab and bendamustine was well tolerated and induced responses in the majority of patients with relapsed indolent B-NHL. NCI Clinical Trials Network registration: NCT01317901.

A screen of zebrafish mutants identifies ethanol-sensitive genetic loci.

BACKGROUND: Fetal alcohol spectrum disorders (FASD) are a highly variable set of phenotypes caused by fetal alcohol exposure. Numerous factors influence FASD phenotypes, including genetics. The zebrafish is a powerful vertebrate model system with which to identify these genetic factors. Many zebrafish mutants are housed at the Zebrafish International Resource Center (ZIRC). These mutants are readily accessible and an excellent source to screen for ethanol (EtOH)-sensitive developmental structural mutants. METHODS: We screened mutants obtained from ZIRC for sensitivity to EtOH teratogenesis. Embryos were treated with 1% EtOH (41 mM tissue levels) from 6 hours postfertilization onward. Levels of apoptosis were evaluated at 24 hours postfertilization. At 4 days postfertilization, the craniofacial skeleton, peripheral axon projections, and sensory neurons of neuromasts were examined. Fish were genotyped to determine whether there were phenotype/genotype correlations. RESULTS: Five of 20 loci interacted with EtOH. Notable among these was that vangl2, involved in convergent extension movements of the embryonic axis, interacted strongly with EtOH. Untreated vangl2 mutants had normal craniofacial morphology, while severe midfacial defects including synophthalmia and narrowing of the palatal skeleton were found in all EtOH-treated mutants and a low percentage of heterozygotes. The cell cycle gene, plk1, also interacted strongly with EtOH. Untreated mutants have slightly elevated levels of apoptosis and loss of ventral craniofacial elements. Exposure to EtOH results in extensive apoptosis along with loss of neural tissue and the entire craniofacial skeleton. Phenotypes of hinfp, mars, and foxi1 mutants were also exacerbated by EtOH. CONCLUSIONS: Our results provide insight into the gene-EtOH interactions that may underlie EtOH teratogenesis. They support previous findings that EtOH disrupts elongation of the embryonic axis. Importantly, these results show that the zebrafish is an efficient model with which to test for gene-EtOH interactions. Understanding these interactions will be crucial to understanding of the FASD variation.

Recent sexual victimization and drinking behavior in newly matriculated college students: a latent growth analysis.

College matriculation is a time of developmental and social change and is often a time of heavy drinking. Sexual victimization (SV) is prevalent in late adolescence and poses additional risk for problem drinking behavior. Thus, matriculating students with a SV history may be at heightened risk for maladaptive alcohol use while transitioning through the first year of college. Furthermore, victimization that has occurred close to college matriculation may confer particular risk for problem alcohol use, because the added stressor of coping with a SV while negotiating the transition into college may lead to risky drinking behavior. Therefore, examining the influence of SV timing (i.e., recency) on drinking patterns in freshman year was the aim of the present study. Matriculating undergraduates with a history of SV were assessed at six points during freshman year. Using latent growth curve modeling, we tested differences in trajectories of drinking behavior (i.e., alcohol use, binge drinking) between students who reported a recent SV and those who reported a more distal SV. Students endorsing a recent SV evidenced greater overall levels of alcohol use and higher levels of binge drinking than individuals with SV that was less recent. Moreover, the recent SV group showed significantly more variability in drinking outcomes over freshman year, with escalations mapping onto more salient periods of transition over the first college year. SV that occurs close to college entry is associated with specific and persistent risk for maladaptive drinking behavior in newly matriculated college students.

The effects of interruptions on oncologists' patient assessment and medication ordering practices.

Interruptions are causal factors in medication errors. Although researchers have assessed the nature and frequency of interruptions during medication administration, there has been little focus on understanding their effects during medication ordering. The goal of this research was to examine the nature, frequency, and impact of interruptions on oncologists' ordering practices. Direct observations were conducted at a Canadian cancer treatment facility to (1) document the nature, frequency, and timing of interruptions during medication ordering, and (2) quantify the use of coping mechanisms by oncologists. On average, oncologists were interrupted 17 % of their time, and were frequently interrupted during safety-critical stages of medication ordering. When confronted with interruptions, oncologists engaged/multitasked more often than resorting to deferring/blocking. While some interruptions are necessary forms of communication, efforts must be made to reduce unnecessary interruptions during safety-critical tasks, and to develop interventions that increase oncologists' resiliency to inevitable interruptions.

Prospective effects of method of coercion in sexual victimization across the first college year.

Women who enter college with a sexual victimization (SV) history may be at particular risk for deleterious outcomes including maladaptive alcohol involve posttraumatic stress, and re-victimization. Further, pre-college SV may be an impediment for the achievement of academic mile and may negatively impact the transition into college. Recent work shows that the method of coercion used in SV may be an important predictor of post-victimization outcomes. As such, the identification of pathways between type of SV and outcomes can aid in early identification and intervention for those at highest risk. In a sample of newly-matriculated female college students, this study examined unique outcomes associated with two specific types of SV, (1) threats/use of physical force (Force SV) or (2) incapacitation (Incap SV). Participants completed assessments of SV, alcohol involvement, posttraumatic stress, and academic outcomes at 6 time-points over their first year of college. Results showed differential outcomes based on pre-matriculation exposure to Force SV or Incap SV. Women with Incap SV were higher on problem drinking indices whereas women with Force SV were at greater risk for re-victimization and marginally more PTSD symptoms. Having a history of either type of SV predicted attrition, but there were no differences when comparing Force SV to Incap SV. Overall, results from this study support the utility of delineating SV experiences by method of coercion, and point to the potential of highlighting different outcomes in tailored intervention programs.

Safety in home care: A research protocol for studying medication management.

BACKGROUND: Patient safety is an ongoing global priority, with medication safety considered a prevalent, high-risk area of concern. Yet, we have little understanding of the supports and barriers to safe medication management in the Canadian home care environment. There is a clear need to engage the providers and recipients of care in studying and improving medication safety with collaborative approaches to exploring the nature and safety of medication management in home care. METHODS: A socio-ecological perspective on health and health systems drives our iterative qualitative study on medication safety with elderly home care clients, family members and other informal caregivers, and home care providers. As we purposively sample across four Canadian provinces: Alberta (AB), Ontario (ON), Quebec (QC) and Nova Scotia (NS), we will collect textual and visual data through home-based interviews, participant-led photo walkabouts of the home, and photo elicitation sessions at clients' kitchen tables. Using successive rounds of interpretive description and human factors engineering analyses, we will generate robust descriptions of managing medication at home within each provincial sample and across the four-province group. We will validate our initial interpretations through photo elicitation focus groups with home care providers in each province to develop a refined description of the phenomenon that can inform future decision-making, quality improvement efforts, and research. DISCUSSION: The application of interpretive and human factors lenses to the visual and textual data is expected to yield findings that advance our understanding of the issues, challenges, and risk-mitigating strategies related to medication safety in home care. The images are powerful knowledge translation tools for sharing what we learn with participants, decision makers, other healthcare audiences, and the public. In addition, participants engage in knowledge exchange throughout the study with the use of participatory data collection methods.

Perceived control and immune and pulmonary outcomes in children with asthma.

OBJECTIVE: This study tested the relationships between perceived control and biological processes relevant to asthma in children. METHODS: Forty children diagnosed with asthma completed the Children's Health Locus of Control (CHLC) scale. Participants also completed pulmonary function testing, measuring forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV1). Blood was drawn to assess immune markers associated with asthma. Specifically, stimulated production of the cytokines interleukin 4 (IL-4), interleukin-5 (IL-5), interleukin-13 (IL-13), interferon-gamma (IFN-gamma), as well as eosinophil count, was measured. At home, participants completed peak expiratory flow rate (PEFR) measures to monitor their daily pulmonary function. RESULTS: Higher levels of perceived control were associated with significantly better FVC, FEV1, and PEFR variability. Higher levels of perceived control were also associated with decreased production of asthma-related cytokines, including IL-4, IL-5, and IL-13. CONCLUSION: These results suggest that psychological processes such as perceived control may play an important role in asthma-related biological processes among children with asthma.

Socioeconomic status and inflammatory processes in childhood asthma: the role of psychological stress.

BACKGROUND: Although social environment variables such as socioeconomic status (SES) have been linked to childhood asthma, little is known about the psychobiological mechanisms underlying this relationship. OBJECTIVES: The goal of this study was to investigate relationships among SES, psychological stress, and immune processes implicated in asthma. METHODS: Thirty-seven children ages 9 to 18 years, physician-diagnosed with asthma, and 39 healthy children participated. Families were interviewed about chronic life stress, perceptions of threat, and SES. Blood samples were drawn from children to assess stimulated production of cytokines implicated in asthma (IL-4, IL-5, IL-13) and eosinophil counts. RESULTS: In children with asthma, lower SES was associated with heightened production of IL-5 and IL-13 and higher eosinophil counts (P values < .05). Lower SES also was associated with higher chronic stress and perceived threat (both groups: P values < .05). Higher levels of stress and threat perception were associated with heightened production of IL-5 and IL-13, and higher eosinophil counts in children with asthma (P values < .05). Statistical mediation tests revealed that chronic stress and threat perception represented statistically significant pathways between SES and immune processes in children with asthma (P values < .05). In healthy children, associations were in the opposite direction from the asthma group, though generally not significant. CONCLUSION: This is one of the first studies to document empirically a psychobiological explanation for the epidemiologic relationship between low SES and poor asthma outcomes. CLINICAL IMPLICATIONS: Associations among SES, psychological stress, and immune pathways suggest that the experience of stress, particularly among lower SES children, has implications for childhood asthma morbidity.