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The yeast INO80 chromatin remodeling complex plays essential roles in regulating DNA damage repair, replication, and promoter architecture. INO80's role in these processes is likely related to its ability to slide nucleosomes, but the underlying mechanism is poorly understood. Here we use ensemble and single-molecule enzymology to study INO80-catalyzed nucleosome sliding. We find that the rate of nucleosome sliding by INO80 increases ∼100-fold when the flanking DNA length is increased from 40 to 60bp. Furthermore, once sliding is initiated, INO80 moves the nucleosome rapidly at least 20bp without pausing to re-assess flanking DNA length, and it can change the direction of nucleosome sliding without dissociation. Finally, we show that the Nhp10 module of INO80 plays an auto-inhibitory role, tuning INO80's switch-like response to flanking DNA. Our results indicate that INO80 is a highly processive remodeling motor that is tightly regulated by both substrate cues and non-catalytic subunits.

This paper aims to highlight the important role of the social work supervision relationship and professional code of ethics for establishing and developing social work values in new graduates as part of practitioner development. In order to achieve this a case study is presented regarding the experience of a first-year, Australian, social work undergraduate faced with attempting to balance professional social work values with those of another discipline and client goals. A discussion takes place regarding the process of resolving the ethical practice dilemma, using the lens of the Solution Focused framework in supervision and the Australian Association of Social Work (AASW) ‘Code of Ethics’ during critical reflection processes. The ethical dilemma presented provides a catalyst to identify how these practices provide core frameworks for developing new social work practitioners. Finally, a brief discussion will take place regarding future research in the area of new social work graduate experiences and the ...

Molecular profiling of human cancer is complicated by both stromal contamination and cellular heterogeneity within samples from tumor biopsies. In this study, we developed a tissue-processing protocol using mechanical dissociation and flow cytometric sorting that resulted in the respective enrichment of stromal and tumor fractions from frozen pancreatic adenocarcinoma samples. Molecular profiling of DNA from the sorted populations using high-density single nucleotide polymorphism arrays revealed widespread chromosomal loss of heterozygosity in tumor fractions but not in either the stromal fraction or unsorted tissue specimens from the same sample. Similarly, a combination of KRAS mutations and chromosomal copy number changes at key pancreatic cancer loci, such as CDK2NA and TP53, was detected in a substantial proportion of the tumor fractions but not in matched stromal fractions from the same sample. This approach to tissue processing could greatly expand the amount of archived tissue that is available for molecular profiling of human cancer and enable a more accurate diagnosis of genetic alterations in patient samples.

A multimedia virtual patient module, involving the case of a young woman with mild intellectual disabilities with a complaint of diffuse abdominal pain, was developed as a clinical training tool for students in health care professions. Primary objectives following use of the module included improved knowledge and reduced perception of difficulty in treating women's health patients with intellectual disabilities. The module was developed using an iterative, collaborative process of a core development team that included medical professionals, multimedia specialists, the parent of a child with intellectual disability, and a disability advocate. Over the course of the module, students were required to identify appropriate and effective clinician-patient interactions in addition to relevant medical and developmental concerns for this patient population. Pilot data from a sample of nursing, physician assistant, and medical students suggest that the module is an effective tool for both improving students' knowledge and reducing their perception of difficulty in providing care to women's health patients with intellectual disabilities.

While the life-threatening nature of severe chemical burns requires an immediate focus on the physical status, long-term psychological functioning in these patients with now concurrent pathology often receives much less attention. A variety of reactions and adjustment issues may present following a burn injury. Treating the psychological aspects is often complicated and difficult, but even more so when the patient has pre-existing psychiatric illness. The current article describes the psychological treatment of an African American patient with chemical burn and significant pre-existing psychopathology in a community mental health setting. The authors purport that a comprehensive treatment approach to burn related injury should include significant attention to cognitive, behavioral, affective, and medical symptoms often in the context of pre-existing symptoms. Secondly, psychological interventions administered by trained mental health professionals are essential therapies to address long-term psychological functioning. Finally, mental health professionals should be considered a functional part of the treatment team in all stages of the burn injury management program particularly with patients who may have pre-existing psychiatric illnesses.

Blacks experience disproportionately elevated rates of tobacco-related morbidity and mortality. Blacks experience delayed smoking initiation relative to other racial/ethnic groups, highlighting the importance of examining smoking correlates occurring in late adolescence/early adulthood. The current study reports data collected as part of an ongoing collaborative effort to assess alcohol and drug use on the campuses of historically black colleges and universities (HBCUs). Two-thousand, two-hundred, seventy-seven African-American subjects, aged 20.3 ± 3.9 (range 18-53), completed the CORE Alcohol and Drug survey and a brief demographic questionnaire. Results indicated that 90% of all subjects overestimated the rate of smoking among their peers. Overestimating was associated with a > 80% increase in the risk of smoking. These data highlight the need to correct misinformation regarding smoking norms among students at some HBCUs.

Nurses play a vital role in providing health care to children with developmental disability (DD) throughout the United States. Unfortunately, most nurses continue to report that they receive little or no clinical education in the area of DDs. In response to this need, a core development team consisting of nurse practitioners and nursing faculty from three universities, one physician assistant faculty, parents of children with DD, and educational specialists developed two multimedia (virtual patient) pediatric instructional modules in CD-ROM format--one involving a child with Down syndrome, and the other involving an infant born at 26 weeks' gestation. Participants were required to make clinical decisions throughout the cases. The modules on CD were piloted with nursing students from three universities. Results of the effectiveness study demonstrated significant gains in knowledge and comfort level regarding the care of children with DD.

The long-term responses of trees to elevated CO2 are especially crucial (1) to mitigating the rate of atmospheric CO2 increase, (2) to determining the character of future forested natural ecosystems and their spread across the landscape, and (3) to determining the productivity of future agricultural tree crops. Therefore, a long-term CO2-enrichment experiment on sour orange trees was started in 1987, and the final results after 17 years are reported herein. Four sour orange trees (Citrus aurantium L.) were grown from seedling stage at 300lmolmol � 1 CO2 above ambient in open-top, clear-plastic-wall chambers at Phoenix, AZ. Four control trees were similarly grown at ambient CO2. All trees were supplied ample water and nutrients comparable with a commercial orchard. After a peak 2‐4 years into the experiment, there was a productivity plateau at about a 70% enhancement of annual fruit and incremental wood production over the last several years of the experiment. When summed over the duration of the experiment, there was an overall enhancement of 70% of total biomass production. Much of the enhancement came from greater numbers of fruits produced, with no change in fruit size. Thicker trunks and branches and more branches and roots were produced, but the root/shoot ratio was unaffected. Also, there was almost no change in the elemental composition of the biomass produced, perhaps in part due to the minimal responsiveness of root-symbiotic arbuscular mycorrhizal fungi to the treatment.

Coenzyme Q10 (CoQ10) is a powerful antioxidant that buffers the potential adverse consequences of free radicals produced during oxidative phosphorylation in the inner mitochondrial membrane. Oxidative stress, resulting in glutathione loss and oxidative DNA and protein damage, has been implicated in many neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. Experimental studies in animal models suggest that CoQ10 may protect against neuronal damage that is produced by ischemia, atherosclerosis and toxic injury. Though most have tended to be pilot studies, there are published preliminary clinical trials showing that CoQ10 may offer promise in many brain disorders. For example, a 16-month randomized, placebo-controlled pilot trial in 80 subjects with mild Parkinson's disease found significant benefits for oral CoQ10 1,200 mg/day to slow functional deterioration. However, to date, there are no published clinical trials of CoQ10 in Alzheimer's disease. Available data suggests that oral CoQ10 seems to be relatively safe and tolerated across the range of 300–2,400 mg/day. Randomized controlled trials are warranted to confirm CoQ10's safety and promise as a clinically effective neuroprotectant.

Patients with advanced cancer may benefit from end of life (EOL) planning, but there is evidence that their willingness and desire to engage in advance care planning (ACP) varies. The reasons for this remain poorly understood. Previous reviews on ACP most commonly report outcome measures related to medical interventions and type of care. Synthesis of the literature, which aims to illuminate the salient characteristics of ACP and investigates the psychological and social features of preparation for the EOL, is required.We searched Medline, EMBASE, PsychINFO, CINAHL, and the Cochrane Central Register of Controlled Trials for studies on perceptions or experiences regarding ACP of adults with cancer, family, friends, or professionals caring for this group. Databases were searched from earliest records to 19 November 2014. A thematic analysis of the literature generated conceptual themes.Of the 2483 studies identified, 40 were eligible for inclusion. Studies addressed the relational nature of ACP, fear surrounding ACP, the conceptual complexity of autonomy, and the influence of institutional culture and previous healthcare experiences on ACP.The complex social and emotional environments within which EOL planning is initiated and actioned are not sufficiently embedded within standardized ACP. The notion that ACP is concerned principally with the 'right' to self-determination through control over treatment choices at the EOL may misrepresent the way that ACP actually occurs in cancer care and ultimately conflict with the deeper concerns and needs of patients, who experience ACP as relational, emotional, and social.

Susceptibility genes for Alzheimer's disease are proving to be highly challenging to detect and verify. Population heterogeneity may be a significant confounding factor contributing to this difficulty. To increase the power for disease susceptibility gene detection, we conducted a genome-wide genetic linkage screen using individuals from the relatively isolated, genetically homogeneous, Amish population. Our genome linkage analysis used a 407-microsatellite-marker map (average density 7 cM) to search for autosomal genes linked to dementia in five Amish families from four Midwestern U.S. counties. Our highest two-point lod score (3.01) was observed at marker D4S1548 on chromosome 4q31. Five other regions (10q22, 3q28, 11p13, 4q28, 19p13) also demonstrated suggestive linkage with markers having two-point lod scores >2.0. While two of these regions are novel (4q31 and 11p13), the other regions lie close to regions identified in previous genome scans in other populations. Our results identify regions of the genome that may harbor genes involved in a subset of dementia patients, in particular the North American Amish community.

Aquakleen® is a common herbicide used to control invasive aquatic plants, and its active ingredient is the butoxyethyl ester of 2, 4-dichlorophenoxyacetic acid (2, 4-D). The effects of 2, 4-D on brook trout (Salvelinus fontinalis), walleye (Sander vitreus), fathead minnow (Pimephales promelas), and the amphipod Hyallela azteca were observed in static acute toxicity tests in the laboratory. The 96-hr LC5Os for brook trout, walleye, and fathead minnow were respectively 0.76, 0.66, and 2.22 mg/L. The 48-hr LC50 for H. azteca was 0.60 mg/L. During three summers in two different lakes, juvenile walleye, brook trout, and/or fathead minnow held in screened enclosures were exposed to 2, 4-D in a controlled manner when the lakes were selectively treated with the herbicide for routine plant control. Reference fishes held in untreated areas of the lakes were also monitored. Mortalities offish of all species after one week were variable but were not significantly different between reference and treated fish ...

Sickle cell disease (SCD) is the most common genetic disorder of the blood. The disease produces significantly abnormal hemoglobin (Hgb) molecules in red blood cells (RBCs). The sickling of RBCs occurs when partially or totally deoxygenated Hgb molecules distort their normal disk shape, producing stiff, sticky, sickle-shaped cells that obstruct small blood vessels and produce vasoocclusion as well as the disruption of oxygen to body tissues. Because tissue damage can occur at multiple foci, patients with SCD are at risk for other medical complications including, but not limited to, delayed growth and sexual maturation; acute and chronic pulmonary dysfunction; stroke; aseptic necrosis of the hip, shoulders, or both; sickle cell retinopathy; dermal ulcers; and severe chronic pain. The chronicity of the illness combined with frequent hospitalizations for pain and other medical management can contribute significantly to impaired psychosocial functioning, altered intra- and interpersonal relationships, and reduced quality of life. Unlike previous qualitative reviews of SCD, this article describes the relevant clinical and research data on the relation between psychosocial functioning and SCD in adult and child populations. The authors discuss the significant role of psychosocial issues in the trajectory and management of the disease and conclude that understanding the pathophysiology of SCD without thoroughly understanding the equally important psychosocial influences is misunderstanding SCD.

Aprosody, or flattened speech intonation, is a recognized negative symptom of schizophrenia, though it has rarely been studied from a linguistic/phonological perspective. To bring the latest advances in computational linguistics to the phenomenology of schizophrenia and related psychotic disorders, a clinical first-episode psychosis research team joined with a phonetics/computational linguistics team to conduct a preliminary, proof-of-concept study.Video recordings from a semi-structured clinical research interview were available from 47 first-episode psychosis patients. Audio tracks of the video recordings were extracted, and after review of quality, 25 recordings were available for phonetic analysis. These files were de-noised and a trained phonologist extracted a 1-minute sample of each patient's speech. WaveSurfer 1.8.5 was used to create, from each speech sample, a file of formant values (F0, F1, F2, where F0 is the fundamental frequency and F1 and F2 are resonance bands indicating the moment-by-moment shape of the oral cavity). Variability in these phonetic indices was correlated with severity of Positive and Negative Syndrome Scale negative symptom scores using Pearson correlations.A measure of variability of tongue front-to-back position-the standard deviation of F2-was statistically significantly correlated with the severity of negative symptoms (r=-0.446, p=0.03).This study demonstrates a statistically significant and meaningful correlation between negative symptom severity and phonetically measured reductions in tongue movements during speech in a sample of first-episode patients just initiating treatment. Further studies of negative symptoms, applying computational linguistics methods, are warranted.

Chromatin remodeling complexes are molecular motors that catalyze diverse structural rearrangements of the genetic material in eukaryotic cells. One such motor, human ACF, is involved in many fundamental gene regulatory processes, including transcriptional activation and repression. ACF is composed of a motor subunit called SNF2h, which is shared with several other remodeling complexes, and a non-catalytic subunit called Acf1. Both SNF2h alone and the ACF complex slide nucleosomes, the basic unit of chromatin, along DNA. Despite the prevalence of ACF and related complexes in genomic regulation, much remains unclear about the mechanism of their sliding activity. SNF2h and Acf1 contain a number of “moving parts” that contribute to significant conformational rearrangements of the enzyme during the remodeling cycle, making them challenging to study by ensemble methods. SNF2h and ACF also dimerize on nucleosomes, further complicating their study in asynchronous populations. Single-molecule techniques are therefore particularly well-suited to investigating such a system. We use single-molecule FRET to observe SNF2h and ACF remodeling individual nucleosomes, to address the following questions: (1) How does the Acf1 accessory subunit modify the basic motor properties of SNF2h, especially in terms of processivity, directional commitment, and remodeling efficiency? (2) How do the “moving” parts of SNF2h combine to regulate the basic activity of the motor? (3) How is protomer coordination achieved across the nucleosome to avoid a tug of war, since enzyme monomers do not directly contact each other?

Background and Purpose. Full-time clinical education experiences represent an average of 41% of the total contact hours students spend in physical therapist education programs. As a result, clinical instructors (CIs) assume an influential role in the professional and social development of physical therapist students. Despite this important role, there is a paucity of published literature describing the qualifications and credentials of these individuals. The purpose of this study was to describe the qualifications and credentials of CIs supervising physical therapist students. Subjects. The participants were 255 physical therapists serving as CIs for 85 physical therapist students in the class of 2001 from 2 physical therapist education programs. Methods. Subjects were asked to complete a CI survey at the conclusion of each clinical experience. Survey instruments were returned by 230 of the 255 CIs (90.20% response rate). Each clinical education experience was 8 weeks in length, and the majority (81.57%) occurred at clinical sites in New England (CT, MA, ME, NH, RI, and VT). Results. The typical profile of a CI in our study is a female whose highest earned degree is a bachelor's degree. The typical CI is not a member of the American Physical Therapy Association and is neither a credentialed CI nor a board certified clinical specialist. Based on median responses, the typical CI has over 5 years of clinical practice and 4 years of clinical teaching and has supervised 2 students during the past 12 months. Discussion and Conclusion. Assessing the qualifications and credentials of CIs provides academic programs with a more accurate depiction of the individuals providing supervision to physical therapist students and may be useful information when planning future clinical faculty development activities. Key Words: Clinical education, Clinical instructors, Physical therapist education, Qualifications, Credentials. INTRODUCTION Clinical education is an integral component of a physical therapist education program. The 2000 Biannual Accreditation Report (BAR), completed in April 2000 by 212 accredited and developing physical therapist education programs, reported mat full-time clinical education represents an average of 25.60% of the total weeks of a physical therapist education program and an average of 41% of the total contact hours.1 The BAR defines full-time clinical education as "35 or more hours per week" that a student spends In the clinical setting.2 There is much in the medical and allied health literature to support the assumption that clinical education faculty assume an influential role in the professional and social development of their respective students.3-8 Therefore, it is essential for physical therapist education programs to identify and monitor the qualifications and credentials of the clinicians who assume the role of clinical instructors (CIs) for their students, especially when one considers the significant amount of time that physical therapist students spend in clinical cducation experiences. Background and Purpose Students are supervised on clinical education experiences by 1 or more physical therapists who serve as the students' CIs. The CIs directly instruct and supervise the students' learning in the clinic and adjust the learning environment so that it is appropriate to students' learning styles. Additionally, CIs must assess students' ability to perform physical therapy-related skills and compare their performance of these skills to the expectations of the entry-level clinician and the academic institution's requirements of its students.9 The Commission on Accreditation in Physical Therapy Education (CAPTE) requires academic programs to assess the clinical education faculty and the clinical education program. According to these guidelines, clinical faculty must demonstrate clinical expertise in their area of practice and be effective clinical teachers. …

Date Presented 3/31/2017 This study compared quality of life (QOL) perspectives between persons with amyotrophic lateral sclerosis (PALS) and their caregivers (CG). Results revealed QOL perspective differences between PALS and CG, especially for mental domains; awareness of differences is vital to providing holistic care. Primary Author and Speaker: Stephanie Johnson Additional Authors and Speakers: Katie Faulkner, Bryant Alonso, Haley Jones, Britton Monroe, Leigh Lehman, Pamalyn Kearney

This study explored differences in perspectives on quality of life (QOL) between people affected by amyotrophic lateral sclerosis (ALS) and their caregivers. QOL is often thought of as related to physical limitations, without consideration of other factors (e.g., cognitive, emotional) that may be stronger predictors of QOL in people with long-term degenerative diseases. Because QOL is complex and influenced by multiple factors, people with ALS and their caregivers may have different perspectives on what constitutes QOL. This study investigated potential discrepancies in QOL perspectives between people with ALS and their caregivers. Thirty dyads from the Augusta University Health ALS Clinic completed a measure of QOL, and we compared the results and identified patterns. The most prominent finding was that members of the dyads misunderstood the mental experiences of one another.

Thyroid cancer incidence is increasing, and with it, an increase in total thyroidectomy. There are limited studies comparing outcomes in total thyroidectomy performed in the inpatient versus outpatient setting.The objective of this study was to perform a comparative analysis of risk factors and outcomes of postoperative morbidity and mortality in total thyroidectomy performed as an inpatient versus outpatient surgery.Retrospective cohort study of data from the 2005 to 2014 multi-institutional, risk-adjusted American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. A multivariate regression model with corresponding odds ratios and 95% confidence intervals was used to determine 30-day morbidity and mortality after total thyroidectomies, and also risk factors of postoperative outcomes.From 2005 to 2014, 40,025 total thyroidectomies were performed (48.5% inpatient, 51.5% outpatient). The 30-day complication rate for all total thyroidectomies was 7.74%. Multivariate logistic regression analysis was performed to control for potential confounding variables. Preoperative factors that affected complications rates for inpatient thyroidectomies included: age ≥70, non-Caucasian race, dependent functional status, history of congestive heart failure, smoking history, bleeding disorder, wound infection, and preoperative sepsis (P < 0.05). In addition, preoperative factors affecting complications in thyroidectomy performed as an outpatient surgery included malignant thyroid pathology (P 0.05).We identified a subset of preoperative conditions that affect risk of complications after total thyroidectomy. Recommendations for patient selection for outpatient total thyroidectomies should be modified to account for pre-existing conditions that increase the risk of postoperative morbidity.

Background Human papilloma virus (HPV) is emerging as the primary cause for some head and neck cancers. The objective of this study was to investigate the association between head and neck cancer (HNC) survival and socioeconomic status (SES) in Canada, and to investigate changes in the relationship between HNC survival and SES from 1992 to 2005. Methods Cases were drawn from the Canadian Cancer Registry (1992–2005), and were categorized into three subsites: oropharynx, oral cavity, and “other” (hypopharynx, larynx, and nasopharynx). Demographic and socioeconomic information were extracted from the Canadian Census of Population data for the study period, which included three census years: 1991, 1996 and 2001. We linked cases to income quintiles (InQs) according to patients’ postal codes. Results Overall survival, without controlling for smoking, for oropharyngeal cancer increased dramatically from 1992–2005 in Canada. This increase in survival for oropharynx cancer was eliminated by the introduction of controls for smoking. Survival for all head and neck cancer subsites was strongly correlated with SES, as measured by income quintile, with lower InQ’s having lower survival than higher. Lastly, the magnitude of the difference in survival between the highest and lowest income quintiles increased significantly over the time period studied for oropharynx cancer, but did not statistically significantly change for oral cavity cancer or other head and neck cancers. Conclusions These data confirm a significant impact of socioeconomic deprivation on overall survival for head and neck cancers in Canada, and may provide indirect evidence that HPV-positive head and neck cancers are more common in higher socioeconomic groups.

The incidence of thyroid cancer is increasing in Canada. The purpose of this study was to investigate the following questions. First, what was the magnitude of increased incidence of thyroid cancer in Canada from 1991-2006? Second, is there an association between socioeconomic status (SES) and thyroid cancer incidence in Canada? Third, does the relationship between SES and the incidence of thyroid cancer vary by rural/urban status?Thyroid cancer cases were drawn from the Canadian Cancer Registry. Demographic and socioeconomic information were extracted from the Canadian Census of Population data. We linked cases to income quintiles (InQs) according to patients' postal codes, and categorized place of residence into city, town, or rural. We then performed a negative binomial regression analysis on the incidence of thyroid cancer to identify relationships between these variables.The overall incidence of thyroid cancer in Canada increased by 156% between 1991 and 2006. Incidence was significantly lower among individuals from lower InQs (incidence rate ratio 0.77 for lowest InQ compared to highest). The incidence of thyroid cancer was more than 25% lower in towns or rural areas compared to cities, after controlling for SES and demographic factors. Lastly, when we allowed the relationship between thyroid cancer incidence and geography of residence to vary by SES, we found that the difference in incidence between highest and lowest InQs was significantly larger in cities than in towns and was insignificant in rural areas.Our study confirmed a dramatic increase in thyroid cancer incidence in Canada. Thyroid cancer incidence was significantly higher in higher InQs and in cities. These data support the theory that increased access to imaging is largely responsible for this increased incidence.

We have previously demonstrated the ability of lovastatin, a potent inhibitor of mevalonate synthesis, to induce tumor-specific apoptosis. The apoptotic effects of lovastatin were regulated in part by the integrated stress response (ISR) that regulates cellular responses to a wide variety of stress inducers. A key regulator of the ISR apoptotic response is activating transcription factor 3 (ATF3) and its target gene CHOP/GADD153. In our study, we demonstrate that in multiple lovastatin-resistant clones of the squamous cell carcinoma (SCC) cell line SCC9, lovastatin treatment (1-25 μM, 24 hr) in contrast to the parental line failed to significantly induce ATF3 expression. Furthermore, the SCC-derived cell lines SCC25 and HeLa that are sensitive to lovastatin-induced apoptosis also preferentially induce ATF3 expression compared to resistant breast (MCF-7) and prostate carcinoma (PC3)-derived cell lines. In HeLa cells shRNA targeting ATF3 expression as well as in ATF3-deficient murine embryonic fibroblasts, lovastatin-induced cytotoxicity and apoptosis were attenuated. In ex vivo HNSCC tumors, lovastatin also induced ATF3 mRNA expression in two of four tumors evaluated. Salubrinal, an agent that can sustain the activity of a key regulator of the ISR eIF2α, further increased the expression of ATF3 and demonstrated synergistic cytotoxicity in combination with lovastatin in SCC cells. Taken together, our results demonstrate preferential induction of ATF3 in lovastatin-sensitive tumor-derived cell lines that regulate lovastatin-induced apoptosis. Importantly, combining lovastatin with salubrinal enhanced ATF3 expression and induced synergistic cytotoxicity in SCC cells.

Large-scale DNA deformation is ubiquitous in transcriptional regulation in prokaryotes and eukaryotes alike. Though much is known about how transcription factors and constellations of binding sites dictate where and how gene regulation will occur, less is known about the role played by the intervening DNA. In this work we explore the effect of sequence flexibility on transcription factor-mediated DNA looping, by drawing on sequences identified in nucleosome formation and ligase-mediated cyclization assays as being especially favorable for or resistant to large deformations. We examine a poly(dA:dT)-rich, nucleosome-repelling sequence that is often thought to belong to a class of highly inflexible DNAs; two strong nucleosome positioning sequences that share a set of particular sequence features common to nucleosome-preferring DNAs; and a CG-rich sequence representative of high G+C-content genomic regions that correlate with high nucleosome occupancy in vivo. To measure the flexibility of these sequences in the context of DNA looping, we combine the in vitro single-molecule tethered particle motion assay, a canonical looping protein, and a statistical mechan- ical model that allows us to quantitatively relate the looping probability to the looping free energy. We show that, in contrast to the case of nucleosome occupancy, G+C content does not positively correlate with looping probability, and that despite sharing sequence features that are thought to determine nucleosome affinity, the two strong nucleosome positioning sequences behave markedly dissimilarly in the context of looping. Most surprisingly, the poly(dA:dT)-rich DNA that is often characterized as highly inflexible in fact exhibits one of the highest propensities for looping that we have measured., Comment: Published version and Supporting Information available at: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0075799

To determine if awareness of oral cancer screening correlates with socioeconomic status (SES) and to determine if screening for oral cancer correlates with SES.Data were obtained from the 2008 American National Health Interview Survey (NHIS).Our primary measure of SES was education; additional measures for SES included income, race, health insurance, and immigration status. We performed a logistic regression analysis, controlling for important demographic characteristics.Awareness of oral cancer screening increases with higher education levels (grade 9 OR 0.37 [CI 0.29-0.48], grade 9-12 OR 0.53 [CI 0.44-0.65], high school OR 0.68 [CI 0.59-0.77], higher degree OR 1.13 [CI 0.96-1.34]). Similarly, screening for oral cancer increases with higher education levels (grade 9 OR 0.31 [CI 0.23-0.42], grade 9-12 OR 0.34 [CI 0.26-0.43], high school OR 0.60 [CI 0.52-0.68], higher degree OR 1.41 [CI 1.18-1.67]). We found that race, income, immigration, and health insurance status were statistically significant correlates with oral cancer awareness and screening.Higher SES individuals are more likely to be aware of and screened for oral cancer. This is problematic because oral cancers are more prevalent in low SES groups. Future awareness and screening campaigns should be directed at vulnerable low SES populations.

Designing simulations for higher education requires planning. This chapter explores the use of a design process of an iterative model with frequent evaluation of the process to ensure strong design in blended and flexible learning. Two case studies are used to demonstrate how the ADDIE process is used in an iterative method to develop simulations to teach and refine professional practice in distance learning situations, from both a course and subject perspective. The authors argue that if a strong development and evaluation process is followed, sustainable simulations can be developed. Results show that students have a positive response to simulation use in learning and appreciate a well structured simulation to aid in professional practice development.

Hepatitis B virus (HBV) infection is a leading risk factor for hepatocellular carcinoma (HCC). HBV integration into the host genome has been reported, but its scale, impact and contribution to HCC development is not clear. Here, we sequenced the tumor and nontumor genomes (>80× coverage) and transcriptomes of four HCC patients and identified 255 HBV integration sites. Increased sequencing to 240× coverage revealed a proportionally higher number of integration sites. Clonal expansion of HBV-integrated hepatocytes was found specifically in tumor samples. We observe a diverse collection of genomic perturbations near viral integration sites, including direct gene disruption, viral promoter-driven human transcription, viral-human transcript fusion, and DNA copy number alteration. Thus, we report the most comprehensive characterization of HBV integration in hepatocellular carcinoma patients. Such widespread random viral integration will likely increase carcinogenic opportunities in HBV-infected individuals.

Objective: 1) Learn how the incidence of HPV-related and non-HPV-related Head and Neck Cancers (HNC) in Canada has changed in the time period 1992 to 2008. 2) Learn how the age at diagnosis and overall survival for these cancers in Canada has changed over that period.Method: We used Canadian Cancer Registry Data (1992-2008), categorizing HNCs into 3 groups: (High (HHPV), ie, oropharynx; Moderate (MHPV), ie, oral cavity; and Low (LHPV), ie, larynx); based on the probability that HPV causes the cancer. We calculated age-adjusted incidence, median age at diagnosis, and survival for each category.Results: HHPV cancers increased in incidence at an average annual rate (AAR) of 1.02% (P = .010); MHPV and LHPV cancers decreased at an AAR of 2.38% (P = .000) and 3.67% (P = .000) respectively. The median age at diagnosis for HHPV cancers decreased by an average of 0.23 years/year (P = .000). There was no change for MHPV and an increase for LHPV of 0.10 years/year (P = .008). Survival for patients with HHPV cancers ...

The purpose of this qualitative study was to explore the lived experience of how sensory-related behaviors of children with autism affected family routines. In-depth semi-structured interviews were conducted with four primary caregivers regarding the meaning and impact of their child’s sensory-related behaviors on family routines that occurred inside and outside the home. Findings indicated that sensory behaviors are one factor that limited family participation in work, family and leisure activities; and that parents employed specific strategies to manage individual and family routines in light of the child’s sensory-related behaviors. This information has important implications for professionals who work with families of children with autism to decrease caregiver stress and to increase life satisfaction for the child and family.

This chapter discusses beliefs, perceptions, and programmatic methods that should be considered when developing a cognitive wellness program for diverse populations. Perceptions of cognitive health and behaviors that may enhance cognitive well-being are presented first, followed by examples of programs that have included minority older adults in substantial numbers. A final section provides a list of considerations that researchers, organizations, and community programs can utilize for developing cognitive wellness programs for diverse older adult populations.

To determine if socio-economic status (SES) affects the stage at presentation of head and neck cancer (HNC) patients in Ottawa, Canada. To determine if the method of diagnosis affects the stage at presentation in these patients. We obtained data on SES, method of diagnosis, and stage at presentation for patients presenting to the head and neck cancer clinic at The Ottawa Hospital Regional Cancer Centre (TORCC). We performed a logistic regression analysis using stage at presentation as the dependent variable. We found no statistically significant association between average family income (by postal code) and stage at presentation. We found that oral cancers presented at a later stage compared with other HNCs but that who made the diagnosis was an important factor. Oral cancers diagnosed by a dentist had 3.44 times the odds of being at a later stage than other HNCs (CI 1.01-11.96), but oral cancers diagnosed by other means had 11.42 times the odds of being at a later stage than other HNCs. We found that male patients presented at a later stage than female patients (OR 2.62, CI 1.03-6.63). Finally, former smokers had about 1/3 the odds of presenting at a later stage than current smokers (OR 0.33, CI 0.13-0.84) although nonsmokers were not significantly less likely than current smokers to present later (OR 0.47, CI 0.17-1.32). We found no evidence that in Ottawa, Canada patients of a lower SES with HNC presented at an different stage than patients with higher SES. We found that patients presenting with oral cancers presented at an earlier stage if they were diagnosed by a dentist.

Summary In an earlier study we identified an increased incidence of head and neck cancer (HNC) in individuals with lower socio-economic status (SES) in the United States. The objective of this study was to determine if lower SES is associated with a similar increase in the incidence of HNC in Canadian patients. We obtained data on SES (income, education and immigration status), demographic characteristics, frequency of dental visits and smoking behavior for adult patients residing in the Eastern Ontario region who were referred to the Ottawa Regional Cancer Centre with HNC. We compared the SES and frequency of dental visits of these HNC patients with the SES and frequency of dental visits of a control sample in the same region from the 2004–2005 Statistics Canada Canadian Community Health Survey (CCHS 3.1). We then performed a logistic regression analysis on the combined sample of patients and controls using incidence of HNC as the dependent variable. This allowed us to eliminate confounding variables such as tobacco intake and to isolate the effect of SES, frequency of dental visits, and immigration status on HNC incidence. There was a statistically significant decrease in the incidence of HNC among adults with a higher median family income (OR = 0.5429, CI = [.3352, .8795]). Also, adults with less than grade 8 education had significantly higher rates of HNC than adults who had completed high school (OR 3.65, CI = [1.88, 7.08]). As well, immigrants had a significantly lower incidence of HNC than Canadian born adults (OR = 0.3825, CI = [.2063, .7090]). Lastly, we found that individuals who typically visited a dentist less than once per year had a significantly higher incidence of HNC than individuals who typically visited a dentist at least once per year (OR = 1.69, CI = [1.01, 2.83]). Even when controlling for tobacco intake, the incidence of HNC in Eastern Ontario was higher in patients with lower median family income and less than grade 8 education. It was higher in individuals who visited a dentist less than once per year, and lower in immigrants to Canada. This was similar to what has been observed in the United States. Further study into the reason for this increased incidence of HNC in patients with lower SES is warranted.

Purpose of review Facial transplantation has become a clinical reality, with the successful completion of five procedures to date in France, China, and most recently the United States. The technical and immunological obstacles associated with this procedure have largely been overcome. There is ongoing debate, however, regarding the ethical implications of the procedure. Recent findings The early literature in facial transplantation stressed the ethical concerns regarding the procedure and recommended that the procedure not be attempted. Recently, however, ethicists and surgeons have created strict ethical guidelines regarding patient selection, informed consent, and accurate evaluation of the risks of the procedure – both medical and psychological. Research has demonstrated that individuals would be willing to accept significant risk to undergo facial transplantation, given the devastating nature of facial disfigurement. In addition, no insurmountable technical or immunological obstacles have been identified to prevent the further success of facial transplantation. Summary The ethical issues associated with facial transplantation will be further refined as more experience is gained with the procedure. With these strict ethical guidelines and with significant efforts in patient selection and preoperative counseling, facial transplantation will likely continue to remain a viable option for patients with significant facial disfigurement.

To evaluate the impact of socioeconomic status on the incidence of head and neck cancer using a population-based survey.We employed pooled individual-level data from the US National Institutes of Health Survey for the years 1997 to 2006 inclusive. We performed a logistic regression analysis for four variables of socioeconomic status (marital status, family income, highest level of education achieved, immigration status) and four potential confounding variables (age, race, smoking status, alcohol consumption). The effects of these socioeconomic variables on head and neck cancer were compared with their effects on cancers overall.There was a statistically significant increase in head and neck cancer incidence for adult men with the following characteristics: status as single, never married and education less than high school completion. There was a trend toward higher rates of head and neck cancer with annual family income$20,000 US. No such associations were seen for cancer in general.There is evidence to support the contention that individuals with more disadvantaged socioeconomic status have higher rates of developing head and neck cancer, even after controlling for associated health behaviours such as smoking and alcohol consumption. This work suggests that further study into the effects of socioeconomic deprivation and head and neck cancer is warranted.

Aim To report preliminary results of a randomised controlled trial looking at the effect of a formal advance care planning intervention (ACP) for patients with incurable cancer. Method 334 patients, who have incurable cancer with disease progression after 1st line chemotherapy and an expected survival of 3–12 months, as well as their nominated family or friend, will be randomised to receive usual care or usual care plus ACP. Knowledge of and compliance with end of life wishes will be assessed. Patient and family or friend satisfaction with care, communication with healthcare providers and the mental health outcomes of the family member or friend will also be assessed. Result 95 participant dyads (of 334) have been randomised to the study (data available for 89). Participants had a median age of 63 (SD = 10) with a mean oncologist estimated median survival of 7.7 months (SD = 2.9). At baseline, 24.7% reported any communication at all with their oncologist regarding their EOL care preferences. At 8 week follow up (n = 47), the results were similar at 23.4%. At baseline 55% and at 8 weeks 76.6% reported communication with their family regarding their EOL care. 5.7% at baseline vs 36.2% at 8 weeks had written their wishes down in a formal way. All reported the quality of the ACP discussion to be ‘good’, ‘very good’ or ‘excellent’. Conclusion This study will provide valuable data on end of life communication between patients, family members and oncologists. ACP discussions appear to be acceptable and may be contributing to increased discussion regarding EOL wishes, over time.

Isoniazid is a leading cause of liver injury but it is not clear how many cases are reported or how many clinicians and patients adhere to American Thoracic Society (ATS) guidelines. We collected data on cases of isoniazid hepatotoxicity and assessed adherence to ATS guidelines and reports to the Centers for Disease Control's (CDC) isoniazid severe adverse events program.We analyzed Drug-Induced Liver Injury Network (DILIN) cases considered definite, highly likely, or probable for isoniazid injury from 2004 through 2013. We assessed the delays in isoniazid discontinuance according to ATS criteria and hepatotoxicity severity by Severity Index Score. We checked reporting to the CDC by matching cases based on age, latency, indication, reporting period, and comorbidities.Isoniazid was the second most commonly reported agent in the DILIN, with 69 cases; 60 of these met inclusion criteria. The median age of cases was 49 years (range, 4-68 y), 70% were female, 97% had latent tuberculosis, and 62% were hospitalized. Patients took a median of 9 days to stop taking isoniazid (range, 0-99 days). Thirty-three cases (55%) continued taking isoniazid for more than 7 days after the ATS criteria for stopping were met. Twenty-four cases (40%) continued isoniazid for more than 14 days after meeting criteria for stopping. A delay in stopping was associated with more severe injury (P.05). Of 13 patients who died or underwent liver transplantation, 9 (70%) continued taking isoniazid for more than 7 days after meeting criteria for stopping. Only 1 of 25 cases of isoniazid hepatotoxicity eligible for reporting to the CDC was reported.Poor adherence to ATS guidelines is common in cases of hepatotoxicity and is associated with more severe outcomes including hospitalization, death, and liver transplantation. Isoniazid continues to be a leading cause of DILI in the United States, and its hepatotoxicity is under-reported significantly.

Aim To describe progress of a study that will evaluate in a randomised controlled trial the effect of a formal advance care planning intervention (ACP) on: The documentation and compliance with patients EOL wishes. The quality of death, costs of care and mental health outcomes of nominated family or friends will also be assessed. Method 334 patients, who have incurable cancer with disease progression after 1st line chemotherapy and an expected survival of 3–12 months, as well as their nominated family or friend, will be randomised to receive usual care or usual care plus ACP. Result ACP research can be challenging. 95 participant dyads (of 334) have been randomised to the study (data available for 89). Participants had a median age of 63 (M = 63.3, SD = 10), were married (70%) and non-tertiary educated (83%). The majority identified their ethnicity as Australian (72%). Mean oncologist estimated median survival was 7.7 months (SD = 2.9). Current progress on the study and challenges to implementation of the research and recruitment will be presented, as well as data regarding screening, inclusion and exclusion of participants. Conclusion Barriers to the implementation of ACP research include: availability of skilled staff, standardisation of ACP interventions, cultural, administrative and technical barriers at hospital sites such as reluctance by clinical staff to introduce ACP research to patients and medical record systems which do not support ACP documentation. Barriers to recruitment include: patient refusal due to time barriers and fear of distress, carer refusal and low referral rate from oncologists.

Obiective: To evaluate the efficacy of suction drainage in preventing postoperative hematoma formation in thyroid surgery. Methods: We conducted a meta-analysis using only randomized controlled trials in which the incidence of post-thyroide ctomy hematoma was compared directly in patients with and without suction drains (eight studies since 1980; N = 944). The odds ratio (OR) with respective confidence intervals (CIs) using the fixed effects model was reported. We used an OR < 1.0 as being in favour of treatment (ie, the use of suction drains). Results: In our meta-analysis, there was no statistically significant difference between the rates of post-thyroide ctomy hematoma whether or not suction drains were used when the results were combined using a fixed effects model (OR 1.04, 95% CI-1.93), with p = .90. In this comparison, a fixed effects model was used rather than a random effects model because there was no statistically significant heterogeneity (x^ = 6.26, p = .28). Conclusions: We conclude that the use of suction drains in thyroid surgery to prevent postoperative hematoma is not evidence based. Sommaire

including high resolution monitoring of hydration changes in proteins. In the present study, we evaluated the disease specific hydration behavior of proteins during the thermal destabilization in CSF samples, based on high resolution molecular acoustic measurements. Analysis of the temperature induced hydration changes enabled a specific characterization of different dementia stages versus healthy controls. We validated to potential of molecular acoustic as a new diagnostic approach to aggregation disorders by investigating CSF samples from patients with Mild Cognitive Impairment (MCI) an early form of human dementia. Comparison of the temperature profiles of ultrasonic velocities enabled a statistically significant differentiation of the MCI group from the healthy control group. Subsequent characterization of the ultrasonic velocity profiles by pattern recognition tools led to the differentiation of the MCI group from healthy groups.These results suggests that molecular acoustics represent a new technical solution for the characterization of early stages of neurodegenerative disorders and may provide a new entry point for diagnostic strategies of misfolding disorders

We describe the assembly of a 1-Mb cosmid contig and restriction map spanning the candidate region for Finnish congenital nephrosis (NPHS1) in 19q13.1. The map was constructed from 16 smaller contigs assembled by fingerprinting, a BAC and a PAC clone, and 42 previously unmapped cosmids. In most cases, single-step cosmid walks were sufficient to join two previously assembled contigs, and all but one gap was filled from this cosmid contig library. The remaining gap of about 19 kb was spanned with a single BAC and a single PAC clone. EcoRI mapping of a dense set of overlapping clones validated the assembly of the map and indicated a length of 1040 kb for the contig. This high-resolution clone map provides an ideal resource for gene identification through cDNA selection, exon trapping, and DNA sequencing.