Dose-escalated intensity-modulated radiotherapy in patients with locally advanced laryngeal and hypopharyngeal cancers: ART DECO, a phase III randomised controlled trial.

BACKGROUND: Radical (chemo)radiotherapy offers potentially curative treatment for patients with locally advanced laryngeal or hypopharyngeal cancer. We aimed to show that dose-escalated intensity-modulated radiotherapy (DE-IMRT) improved locoregional control. METHODS: We performed a phase III open-label randomised controlled trial in patients with laryngeal or hypopharyngeal cancer (AJCC III-IVa/b, TNM 7). Patients were randomised (1:1) to DE-IMRT or standard dose IMRT (ST-IMRT) using a minimisation algorithm, balancing for centre, tumour site, nodal status and chemotherapy use. DE-IMRT was 67.2 gray (Gy) in 28 fractions (f) to the primary tumour and 56Gy/28f to at-risk nodes; ST-IMRT was 65Gy/30f to primary tumour and 54Gy/30f to at-risk nodes. Suitable patients received 2 cycles of concomitant cisplatin and up to 3 cycles of platinum-based induction chemotherapy. The primary end-point was time to locoregional failure analysed by intention-to-treat analysis using competing risk methodology. FINDINGS: Between February 2011 and October 2015, 276 patients (138 ST-IMRT; 138 DE-IMRT) were randomised. A preplanned interim futility analysis met the criterion for early closure. After a median follow-up of 47.9 months (interquartile range 37.5-60.5), there were locoregional failures in 38 of 138 (27.5%) ST-IMRT patients and 42 of 138 (30.4%) DE-IMRT patients; an adjusted subhazard ratio of 1.16 (95% confidence interval: 0.74-1.83, p = 0.519) indicated no evidence of benefit with DE-IMRT. Acute grade 2 pharyngeal mucositis was reported more frequently with DE-IMRT than with ST-IMRT (42% vs. 32%). No differences in grade ≥3 acute or late toxicity rates were seen. CONCLUSION: DE-IMRT did not improve locoregional control in patients with laryngeal or hypopharyngeal cancer. The trial is registered: ISRCTN01483375.

The Increased Risk for HIV and Other Sexually Transmitted Infections Among Substance-Using and Depressed Women in the Legal System.

This study was conducted in Alabama's Black Belt Counties to examine the association between household food insecurity and self-reported health status. Data were collected from 400 households to measure household food insecurity and self-reported general health status using the U.S. Food Security Module. In bivariate analyses, household food insecurity was Policy changes to increase economic resources and access to federal food programs are needed to reduce household food insecurity in this region. Gendered experiences in the context of consequences of poverty should not be ignored.

Specialized sledge dogs accompanied Inuit dispersal across the North American Arctic.

Domestic dogs have been central to life in the North American Arctic for millennia. The ancestors of the Inuit were the first to introduce the widespread usage of dog sledge transportation technology to the Americas, but whether the Inuit adopted local Palaeo-Inuit dogs or introduced a new dog population to the region remains unknown. To test these hypotheses, we generated mitochondrial DNA and geometric morphometric data of skull and dental elements from a total of 922 North American Arctic dogs and wolves spanning over 4500 years. Our analyses revealed that dogs from Inuit sites dating from 2000 BP possess morphological and genetic signatures that distinguish them from earlier Palaeo-Inuit dogs, and identified a novel mitochondrial clade in eastern Siberia and Alaska. The genetic legacy of these Inuit dogs survives today in modern Arctic sledge dogs despite phenotypic differences between archaeological and modern Arctic dogs. Together, our data reveal that Inuit dogs derive from a secondary pre-contact migration of dogs distinct from Palaeo-Inuit dogs, and probably aided the Inuit expansion across the North American Arctic beginning around 1000 BP.

Public Health and Interprofessional Education as Critical Components in the Evolution of Osteopathic Medical Education.

Public health and interprofessional education (IPE) are included among the osteopathic core competencies and Entrustable Professional Activities that should be reflected in osteopathic medical curricula. Cognizant of the importance of these 2 areas, Touro University College of Osteopathic Medicine-CA (TUCOM) has developed initiatives to advance them on campus as well as within its academic curriculum. The authors acknowledge the importance of incorporating public health content into osteopathic medicine as well as expanding IPE in the health professions as part of a larger project to impart a unique identity and relevance to osteopathic medical education at TUCOM. The authors describe TUCOM's public health and IPE initiatives and outcomes in the context of current and future relevance for osteopathic medicine. Future directions to assess the quality and impact of these programs that may be of value for other colleges of osteopathic medicine are also discussed.

Patient preferences and access to text messaging for health care reminders in a safety-net setting.

INTRODUCTION: Text messaging may be an effective method for providing health care reminders to patients. We aimed to understand patient access to and preferences for receiving health-related reminders via text message among patients receiving care in safety-net hospitals. MATERIALS AND METHODS: We conducted face-to-face surveys with 793 patients seeking care in three hospital emergency departments at a large safety-net institution and determined clinical and demographic predictors of preferences for text messaging for health care reminders. RESULTS: 95% of respondents reported having daily access to text messaging. Text messaging was preferred over e-mail, phone, and letters for communication. 78% of respondents wanted to receive appointment reminders, 56% wanted expiring insurance reminders, and 36% wanted reminders to take their medications. We found no clinical predictors but did find some demographic predictors-including age, ethnicity, insurance status, and income-of wanting text message reminders. DISCUSSION: In our convenience sample of safety-net patients, text messaging is an accessible, acceptable, and patient-preferred modality for receiving health care reminders. Text messaging may be a promising patient-centered approach for providing health care and insurance reminders to patients seeking care at safety-net institutions.

Integrating archaeology and ancient DNA analysis to address invasive species colonization in the Gulf of Alaska.

The intentional and unintentional movement of plants and animals by humans has transformed ecosystems and landscapes globally. Assessing when and how a species was introduced are central to managing these transformed landscapes, particularly in island environments. In the Gulf of Alaska, there is considerable interest in the history of mammal introductions and rehabilitating Gulf of Alaska island environments by eradicating mammals classified as invasive species. The Arctic ground squirrel (Urocitellus parryii) is of concern because it affects vegetation and seabirds on Gulf of Alaska islands. This animal is assumed to have been introduced by historic settlers; however, ground squirrel remains in the prehistoric archaeological record of Chirikof Island, Alaska, challenge this timeline and suggest they colonized the islands long ago. We used 3 lines of evidence to address this problem: direct radiocarbon dating of archaeological squirrel remains; evidence of prehistoric human use of squirrels; and ancient DNA analysis of dated squirrel remains. Chirikof squirrels dated to at least 2000 years ago, and cut marks on squirrel bones suggested prehistoric use by people. Ancient squirrels also shared a mitochondrial haplotype with modern Chirikof squirrels. These results suggest that squirrels have been on Chirikof longer than previously assumed and that the current population of squirrels is closely related to the ancient population. Thus, it appears ground squirrels are not a recent, human-mediated introduction and may have colonized the island via a natural dispersal event or an ancient human translocation.

Influence of Bovine Whey Protein Concentrate and Hydrolysate Preparation Methods on Motility in the Isolated Rat Distal Colon.

Whey protein concentrate (WPC) and hydrolysate (WPH) are protein ingredients used in sports, medical and pediatric formulations. Concentration and hydrolysis methods vary for whey sourced from cheese and casein co-products. The purpose of this research was to investigate the influence of whey processing methods on in vitro gastrointestinal (GI) health indicators for colonic motility, epithelial barrier integrity and immune modulation. WPCs from casein or cheese processing and WPH (11% or 19% degree of hydrolysis, DH) were compared for their effects on motility in a 1 cm section of isolated rat distal colon in an oxygenated tissue bath. Results showed that WPC decreased motility irrespective of whether it was a by-product of lactic acid or mineral acid casein production, or from cheese production. This indicated that regardless of the preparation methodology, the whey protein contained components that modulate aspects of motility within the distal colon. WPH (11% DH) increased contractile frequency by 27% in a delayed manner and WPH (19% DH) had an immediate effect on contractile properties, increasing tension by 65% and frequency by 131%. Increased motility was associated with increased hydrolysis that may be attributed to the abundance of bioactive peptides. Increased frequency of contractions by WPH (19% DH) was inhibited (by 44%) by naloxone, implicating a potential involvement of opioid receptors in modulation of motility. Trans-epithelial electrical resistance and cytokine expression assays revealed that the WPC proteins studied did not alter intestinal barrier integrity or elicit any discernible immune response.

Avanex Unique Endophyte Technology: Reduced Insect Food Source at Airports.

Birds and other forms of wildlife are a major issue for airport authorities worldwide, as they can create hazards to operating aircraft. Wildlife "strikes," the majority caused by birds, can cause damage to operating aircraft and in severe cases lead to a loss of human life. Many airfields contain large areas of ground cover herbage alongside their runways that consist of mixtures of grasses, legumes, and weeds that can harbor many invertebrates. Many airfields use insecticides to control insect populations; however, mounting pressure from regional councils and water boards aim to reduce this practice due to ground water runoff and contamination concerns. Avanex Unique Endophyte Technology, a product specifically developed to reduce the attractiveness of airports and surrounding areas to birds, is based on a novel association between a selected strain of Epichloë endophyte and a turf-type tall fescue cultivar. This grass-endophyte association acts through a direct mechanism whereby a negative response in birds is created through taste aversion and postingestion feedback as well as an indirect mechanism by deterring many invertebrates, a food source of many bird species.

Variation in the expression of ergot alkaloids between individual tillers of perennial ryegrass.

Epichloë fungal endophytes of cool season grasses are well-known to produce a range of alkaloids of benefit to the host. Some of these compounds are advantageous to agriculture due to qualities that promote pasture persistence (e.g., the loline class of alkaloids confer insect protection) while others are detrimental to the well-being of grazing livestock. The ergot alkaloids (e.g., ergovaline), produced in ryegrass and tall fescue associations, causes poor animal health in farming regions in many countries around the world and further study is required to improve our knowledge on this class of compounds. Here we present the application of a quantitative LC-MS/MS (liquid chromatography coupled to mass spectrometry) method measuring eight ergot alkaloids (chanoclavine, agroclavine, elymoclavine, lysergol, lysergic acid, ergine, lysergyl-alanine, ergovaline) produced by endophyte infected grasses, to monitor levels in individual tillers from multiple plants of a single cultivar of perennial ryegrass (Lolium perenne cv. "Grasslands Samson") infected with a common toxic endophyte strain (Epichloë festucae var. lolii). Monitoring the expression in individual tillers allows an estimation of the variability within a plant (between tillers) as well as between plants. The study showed that there is significant variation in the concentration of the ergot alkaloids between tillers of a single plant, at or exceeding the level of variation observed between individual plants of a population. This result emphasizes the fundamental importance of robust experimental design and sampling procedures when alkaloid expression assessment is required and these need to be rigorously tailored to the hypothesis being tested.

Assessment of fluorescein-based fluorescent dyes for tracing Neotyphodium endophytes in planta.

Fluorescent dyes were assessed for their ability to stain viable hyphae of the fungi Neotyphodium lolii and N. coenophialum, symbiotic endophytes of the Pooideae grasses Lolium perenne and Festuca arundinacea, respectively. The fluorescein-based fluorophores; fluorescein diacetate (FDA), 5(6)-carboxy-fluorescein diacetate (CFDA), 5-chloromethylfluorescein diacetate (CMFDA) and the chitin-binding stain, Calcofluor while M2R, were assessed for staining of endophyte hyphae in vitro from axenic fungal cultures and in planta, including epidermal leaf sheath peels, nodes, ovaries, embryos and meristems. CMFDA produced the greatest intensity of staining of fungal hyphae and gave excellent contrast in planta compared to the plant cells. Compared to the other dyes, CMFDA was also the least affected by photo bleaching and continued to fluoresce up to 2 h after initial excitation. None of the fluorescent dyes stained fungal hyphae in seed.

The use of and satisfaction with the Emergency Severity Index.

INTRODUCTION: The Emergency Severity Index (ESI) is a 5-level emergency department triage algorithm designed to facilitate the sorting and streaming of patients. The purpose of this study was to assess the use of the ESI in emergency departments, including satisfaction with the ESI, usefulness of the ESI compared with other triage algorithms, and lessons learned from implementation. METHODS: A self-administered questionnaire was sent to 935 people who requested the ESI training materials from the Agency for Healthcare Research and Quality (AHRQ) at the U.S. Department of Health and Human Services and who volunteered to participate in a study about the ESI. The response rate for the survey was 42% (n = 392). Telephone interviews were conducted with an additional 19 ED professionals. Descriptive statistics and qualitative content analysis were used in the data analysis. RESULTS: Three hundred twenty-two survey respondents (82%) reported that they use the ESI in their emergency department. Satisfaction with the ESI triage algorithm is high. ESI users indicated that the ESI is more accurate than other triage algorithms and that its strengths are simplicity of use and the ability to reduce the subjectivity of triage. DISCUSSION: The majority of ED professionals who reported using the ESI were very satisfied with the tool. Users found that it was more accurate than other triage algorithms and reduced the subjectivity of the triage process. Both survey and interview findings indicated that few emergency departments have formally assessed the impact of the ESI on ED operations.

A crisis in the making? Education, ageing populations and the future of the medical research workforce.

OBJECTIVES: this study aims to project attrition from the Australian health and medical research workforce for those aged > 40 years in 2009, through to 2019, and to draw conclusions about the future of this workforce and the international implications of ageing workforce populations. METHODS: the study uses recently collected unpublished demographic data on the 2009 health and medical research workforce drawn from an Australian Society for Medical Research survey of health and medical research organisations. RESULTS: about 6250 members of the health and medical research workforce aged > 40 years in 2009 are expected to leave the workforce during 2009-2019; the bulk of these will be aged 50-69 years. It is estimated that 35% of women and 49% of men aged 40-49 years in 2009 will retire by the age of 50-59 years, and 85% of women and 70% of men aged 50-59 years in 2009 are also projected to retire over the next 10 years. Of the 6250 members who are expected to leave the workforce by 2019, about 4000 hold a PhD. As a result of population growth, a further 1700 persons with a PhD will be required if Australia is to maintain its current ratio of PhD-qualified persons in the health and medical research workforce: working population to 2019, at a cost of about AU$240 million. CONCLUSIONS: there is a need to plan for the replacement of the retiring generation of the health and medical research workforce and for the growth required to match that of the working population. If Australia is to fulfil its ambition for a highly educated, optimally skilled and highly trained health and medical research sector, it must heighten its focus on the higher education of young medical researchers. As population ageing is an emerging phenomenon worldwide, all first world nations are likely to face the challenges involved in replacing a rapidly retiring generation of the health and medical research workforce.

Tumour budding and a low host inflammatory response are associated with a poor prognosis in oesophageal and gastro-oesophageal junction cancers.

AIMS: Tumour budding and host inflammatory response are parameters easily assessed histologically that have prognostic significance in many cancers. There have been few studies examining these parameters in oesophageal or gastro-oesophageal cancers. This study aims to address that deficiency. METHODS AND RESULTS: A two-centre, retrospective study was carried out on 356 patients. Tumour budding and host inflammatory response at the invasive front were assessed histologically. Statistical analysis was performed to determine the prognostic significance of these factors. The median number of tumour buds was four (range 0-50) with 172 of 356 cases having five or more buds at the invasive front. The presence of five or more buds was associated with a poor prognosis on univariate analysis (P = 0.0001), as was a sparse or moderate host inflammatory response (P = 0.001). Tumour budding retained prognostic significance when tumours were separated into adenocarcinomas (n = 287) and squamous cell carcinomas (n = 69), but host inflammatory response was a significant prognostic factor only for adenocarcinomas. On multivariate analysis the presence of five or more buds retained significance (P = 0.002). CONCLUSIONS: Tumour budding and host inflammatory response are important prognostic factors in patients with oesophageal/gastro-oesophageal cancer and can be used to identify high-risk patients who would benefit from closer follow-up and adjuvant therapies.

Normal tissue reactions to radiotherapy: towards tailoring treatment dose by genotype.

A key challenge in radiotherapy is to maximize radiation doses to cancer cells while minimizing damage to surrounding healthy tissue. As severe toxicity in a minority of patients limits the doses that can be safely given to the majority, there is interest in developing a test to measure an individual's radiosensitivity before treatment. Variation in sensitivity to radiation is an inherited genetic trait and recent progress in genotyping raises the possibility of genome-wide studies to characterize genetic profiles that predict patient response to radiotherapy.

Perceptions in health and medical research careers: the Australian Society for Medical Research Workforce Survey.

OBJECTIVE: To report on the sentiments of the Australian health and medical research (HMR) workforce on issues related to employment and funding opportunities. DESIGN, SETTING AND PARTICIPANTS: In August 2006, the Australian Society for Medical Research (ASMR) invited all of its members to participate in an online survey. The survey took the form of a structured questionnaire that focused on career aspirations, career development and training opportunities, attitudes toward moving overseas to work, and employment conditions for medical researchers. MAIN OUTCOME MEASURES: Researchers' views on career opportunities, funding opportunities, salary and quality of the working environment; impact of these views on retaining a skilled medical research workforce in Australia. RESULTS: Of the 1258 ASMR members, 379 responded (30% response rate). Ninety-six per cent of respondents were currently based in Australia; 70% had a PhD or equivalent; and 58% were women. Most respondents worked at hospital research centres (37%), independent research institutes (28%) or university departments (24%). Sixty-nine per cent had funding from the National Health and Medical Research Council, with the remainder funded by other sources. Over the previous 5 years, 6% of respondents had left active research and 73% had considered leaving. Factors influencing decisions about whether to leave HMR included shortage of funding (91%), lack of career development opportunities (78%) and poor financial rewards (72%). Fifty-seven per cent of respondents were directly supported by grants or fellowships, with only 16% not reliant on grants for their continuing employment; 62% believed that funding had increased over the previous 5 years, yet only 30% perceived an increase in employment opportunities in HMR. Among the respondents, twice as many men as women held postgraduate qualifications and earned >or= dollars 100 000 a year. CONCLUSIONS: Employment insecurity and lack of funding are a cause of considerable anxiety among Australian health and medical researchers. This may have important implications for the recruitment and retention of researchers.

Vision and driving self-restriction in older adults.

OBJECTIVES: To assess driving self-restriction (vision related and nonvision related) in relation to vision test performance of older adults. DESIGN: Cross-sectional study. SETTING: Population-based cohort of community-dwelling older adults. PARTICIPANTS: Six hundred twenty-nine current drivers aged 55 and older had driving behavior, health, and physical function assessed and vision function tested in 1993-95. MEASUREMENTS: Self-report of driving restriction as vision or non-vision related and performance on a comprehensive battery of vision tests (visual acuity; contrast sensitivity; effects of illumination level, contrast, and glare on acuity; visual fields with and without attentional load; color vision; temporal sensitivity; and the effect of dim light on walking ability). RESULTS: Demographic, health, and functional characteristics differed significantly between restrictors and nonrestrictors but not between vision- and nonvision-related restrictors. Controlling for potential confounding, only vision-related driving self-restriction was significantly associated with reduced performance on nonstandard measures of acuity. Poor depth perception was significantly associated with restriction for both vision- and nonvision-related reasons. Poor performance on attentional visual field tests, analyzed individually and in combination with standard field tests, was not associated with driving self-restriction. CONCLUSION: Older adults with early changes in spatial vision function and depth perception appear to recognize their limitations and restrict their driving even if they do not acknowledge the visual impairment as the cause for restriction. Poor visual attention, a risk factor for crashes, may not be recognized. Additional studies of driving self-restriction in relation to risk factors for crashes in older adults may help refine this strategy of reducing driving-related injury and death.

Is vision function related to physical functional ability in older adults?

OBJECTIVES: To assess the relationship between a broad range of vision functions and measures of physical performance in older adults. DESIGN: Cross-sectional study. SETTING: Population-based cohort of community-dwelling older adults, subset of an on-going longitudinal study. PARTICIPANTS: Seven hundred eighty-two adults aged 55 and older (65% of living eligible subjects) had subjective health measures and objective physical performance evaluated in 1989/91 and again in 1993/95 and a battery of vision functions tested in 1993/95. MEASUREMENTS: Comprehensive battery of vision tests (visual acuity, contrast sensitivity, effects of illumination level, contrast and glare on acuity, visual fields with and without attentional load, color vision, temporal sensitivity, and the impact of dimming light on walking ability) and physical function measures (self-reported mobility limitations and observed measures of walking, rising from a chair and tandem balance). RESULTS: The failure rate for all vision functions and physical performance measures increased exponentially with age. Standard high-contrast visual acuity and standard visual fields showed the lowest failure rates. Nonstandard vision tests showed much higher failure rates. Poor performance on many individual vision functions was significantly associated with particular individual measures of physical performance. Using constructed combination vision variables, significant associations were found between spatial vision, field integrity, binocularity and/or adaptation, and each of the functional outcomes. CONCLUSIONS: Vision functions other than standard visual acuity may affect day-to-day functioning of older adults. Additional studies of these other aspects of vision and how they can be treated or rehabilitated are needed to determine whether these aspects play a role in strategies for reducing disability in older adults.