Ultrafast dynamics of fluorene initiated by highly intense laser fields.

We present an investigation of the ultrafast dynamics of the polycyclic aromatic hydrocarbon fluorene initiated by an intense femtosecond near-infrared laser pulse (810 nm) and probed by a weak visible pulse (405 nm). Using a multichannel detection scheme (mass spectra, electron and ion velocity-map imaging), we provide a full disentanglement of the complex dynamics of the vibronically excited parent molecule, its excited ionic states, and fragments. We observed various channels resulting from the strong-field ionization regime. In particular, we observed the formation of the unstable tetracation of fluorene, above-threshold ionization features in the photoelectron spectra, and evidence of ubiquitous secondary fragmentation. We produced a global fit of all observed time-dependent photoelectron and photoion channels. This global fit includes four parent ions extracted from the mass spectra, 15 kinetic-energy-resolved ionic fragments extracted from ion velocity map imaging, and five photoelectron channels obtained from electron velocity map imaging. The fit allowed for the extraction of 60 lifetimes of various metastable photoinduced intermediates.

Exploring the ultrafast and isomer-dependent photodissociation of iodothiophenes via site-selective ionization.

C-I bond extension and fission following ultraviolet (UV, 262 nm) photoexcitation of 2- and 3-iodothiophene is studied using ultrafast time-resolved extreme ultraviolet (XUV) ionization in conjunction with velocity map ion imaging. The photoexcited molecules and eventual I atom products are probed by site-selective ionization at the I 4d edge using intense XUV pulses, which induce multiple charges initially localized to the iodine atom. At C-I separations below the critical distance for charge transfer (CT), charge can redistribute around the molecule leading to Coulomb explosion and charged fragments with high kinetic energy. At greater C-I separations, beyond the critical distance, CT is no longer possible and the measured kinetic energies of the charged iodine atoms report on the neutral dissociation process. The time and momentum resolved measurements allow determination of the timescales and the respective product momentum and kinetic energy distributions for both isomers, which are interpreted in terms of rival 'direct' and 'indirect' dissociation pathways. The measurements are compared with a classical over the barrier model, which reveals that the onset of the indirect dissociation process is delayed by ∼1 ps relative to the direct process. The kinetics of the two processes show no discernible difference between the two parent isomers, but the branching between the direct and indirect dissociation channels and the respective product momentum distributions show isomer dependencies. The greater relative yield of indirect dissociation products from 262 nm photolysis of 3-iodothiophene (cf. 2-iodothiophene) is attributed to the different partial cross-sections for (ring-centred) π∗ ← π and (C-I bond localized) σ∗ ← (n/π) excitation in the respective parent isomers.

The effect of a dementia awareness class on changing dementia attitudes in adolescents.

BACKGROUND: Current evidence suggests that negative and stigmatising attitudes towards dementia may develop at a young age. There are a number of dementia education and awareness initiatives aimed at reducing stigma, though they have not been robustly evaluated to establish the impact on dementia attitudes or suitability in adolescent populations. This study explored the efficacy and satisfaction of one such initiative (Dementia Friends) in a British adolescent sample. METHODS: 301 adolescents (M = 12.6 years old, SD = 0.73) were assigned to either receive Dementia Friends (a 60-min interactive class that teaches about dementia and its effects on people's lives) or education as usual. All participants completed a series of validated questionnaires pre- and post-intervention, related to dementia attitudes (Brief A-ADS and KIDS). RESULTS: Adolescents in the dementia awareness group showed little to no improvements between time-points. The change scores in the dementia awareness group did not significantly differ to the control group based on both KIDS (d = - 0.003, p = 0.98) and Brief A-ADS (d = 0.14, p = 0.13) measures. There was no Group x Time effect after controlling for confounding variables. CONCLUSIONS: Dementia Friends is successful in terms of reach and impact, though this study suggests that it may fall short of achieving its goal of improving attitudes towards dementia. Importantly, Dementia Friends did not have a negative effect on attitudes, and the majority of adolescents enjoyed the sessions. It is important that these findings are replicated in a larger randomised-controlled study.

Effect of internal mammary vessels radiation dose on outcomes of free flap breast reconstruction.

To assess the impact of internal mammary (IM) vessels radiation dose on autologous free-flap based breast reconstruction outcomes. We retrospectively evaluated the medical records of breast cancer patients who underwent mastectomy and free-flap breast reconstruction after postoperative radiation therapy (RT) to the breast/chest wall with (n = 9) or without (n = 11) electively including the IM lymph nodes. Twenty patients were included. Median age at diagnosis was 50 years (range, 33-63). The median time interval between the start of RT and reconstructive surgery was 16 months (range, 6-45). The maximal IM vessels dose was not associated with the risk of all complications (P = 0.44) or fat necrosis (P = 0.31). The mean IM vessels dose was not significant for the risk of all complications (P = 0.13) but was significant for fat necrosis (P = 0.04). A high mean IM vessels dose was related to the occurrence of fat necrosis.

Clinical characteristics associated with racial disparities in endometrial cancer outcomes: A surveillance, epidemiology and end results analysis.

OBJECTIVES: Racial disparities exist for endometrial cancer. We examined patterns of care and factors associated with poor outcomes for Black women with endometrial cancer. METHODS: We studied 110,826 endometrial cancer patients diagnosed between 1980 and 2008 with minimum 5years follow-up in the Surveillance, Epidemiology, and End Results database. Trends over time in sociodemographics, disease characteristics and treatment factors were analyzed over four eras: 1980-1989, 1990-1999, 2000-2004, 2005-2008. Using sequential Cox proportional hazards and Fine-Gray competing risk models we determined the association between potential explanatory variables and racial disparities in all-cause mortality (ACM) and cancer-specific mortality (CSM), respectively. RESULTS: Clinical characteristics of Black and White women were relatively constant over time. The unadjusted hazard ratio (HR) among Black women for ACM and CSM were 1.91 (95% CI 1.86-1.97) and 2.35 (95% CI 2.26-2.43), respectively. Adjustment for sociodemographics, disease presentation and surgery decreased the ACM HR to 1.29 (95% CI 1.24-1.34) and CSM HR to 1.18 (95% CI 1.11-1.26) without further decrease from controlling for radiotherapy. Black women were less likely to undergo operative management even when prescribed. Total and radical hysterectomy, and vaginal brachytherapy (VBT) were associated with improved ACM and CSM. Combination VBT and external beam radiotherapy was associated with improved ACM. CONCLUSION: Racial disparities in endometrial cancer survival are predominantly attributable to increased advanced stage, high-grade and aggressive histologic subtype tumors and differential use of surgery in Black women. Intensified surgical and radiation treatment is associated with improved survival, raising questions about treatment adaptations that may potentially reduce survival disparities.

Management of Triple-Negative Breast Cancer in Older Patients: How Is It Different?

Triple-negative breast cancer, which affects about 10% of older women with breast cancer, represents a major treatment challenge in this population. Treatment decisions for these patients can best be made based on geriatric assessment, estimated life expectancy, whether the treatment goal is prolonged survival or palliation, the potential benefits and toxicities of a specific treatment, and the patient's personal goals for treatment. Treatment outcomes for healthy older and younger women are similar, but great challenges exist in managing the vulnerable and frail patient. The cornerstone of therapy for early-stage triple-negative breast cancer is local therapy (surgery and radiation) and, for most patients, adjuvant chemotherapy. In the management of metastatic triple-negative breast cancer, all therapy is palliative and chemotherapy is the treatment of choice. Since all treatment modalities in older patients-especially chemotherapy-can affect physical and mental function, a geriatric assessment is key in selecting the most appropriate treatment strategy. Many older patients (older than 70 years) are poor candidates for state-of-the-art therapy, and some who have substantial comorbidities not related to breast cancer may opt for palliative and hospice care. In this review, we will discuss the role of geriatric assessment, alternative treatment modalities for older women with triple-negative breast cancer, and other special considerations for this patient population.

Pentoxifylline and vitamin E for treatment or prevention of radiation-induced fibrosis in patients with breast cancer.

Radiation therapy (RT) plays an important role in the management of breast cancer. Radiation-induced fibrosis is a side effect of radiation therapy and may occur in up to 13% of the cases in patients (Radiother Oncol, 2009;90:80), fortunately usually is modest/localized and not associated with marked symptoms. However, occasionally, fibrosis can be moderate-to-severe, and cause clinically-meaningful symptoms. The current review summarizes the use of pentoxifylline and vitamin E of treatment or prevention of radiation-induced fibrosis in breast cancer patients. Even though data are limited, this regimen may reduce RT-associated toxicity.

Early cardiac perfusion defects after left-sided radiation therapy for breast cancer: is there a volume response?

PURPOSE: Cardiac single-photon emission computed tomography (SPECT) is often used to identify defects in myocardial perfusion due to atherosclerotic coronary artery disease. It was also used in studies to evaluate radiation therapy (RT)-associated cardiac abnormalities. In the current review, we aim to evaluate the rates of post-RT cardiac SPECT early perfusion abnormalities and relate this to the irradiated left ventricular volume. METHODS: The studies cited in this systematic review were identified using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. RESULTS: Six studies between 1996 and 2016 fulfilled the inclusion criteria. The reported perfusion defects in these studies were seen in the apical and anterolateral aspects of the left ventricle. Three studies show correlation between the percent of the left ventricle within the RT-field and percent of patients with early perfusion defects on cardiac SPECT. In two studies that used cardiac sparing techniques (such as deep inspiration), that resulted in a low mean heart dose, no perfusion defects were noted. CONCLUSIONS: Data suggest that incidental irradiation of the heart in cases of left breast/chest wall RT can result in early post-RT perfusion defects on cardiac SPECT. There appears to be strong dose/volume dependence to the risk, and hence techniques to reduce cardiac exposure are recommended.

Results of a Regional Effort to Improve Warfarin Management.

BACKGROUND: Improved anticoagulation control with warfarin reduces adverse events and represents a target for quality improvement. No previous study has described an effort to improve anticoagulation control across a health system. OBJECTIVE: To describe the results of an effort to improve anticoagulation control in the New England region of the Veterans Health Administration (VA). METHODS: Our intervention encompassed 8 VA sites managing warfarin for more than 5000 patients in New England (Veterans Integrated Service Network 1 [VISN 1]). We provided sites with a system to measure processes of care, along with targeted audit and feedback. We focused on processes of care associated with site-level anticoagulation control, including prompt follow-up after out-of-range international normalized ratio (INR) values, minimizing loss to follow-up, and use of guideline-concordant INR target ranges. We used a difference-in-differences (DID) model to examine changes in anticoagulation control, measured as percentage time in therapeutic range (TTR), as well as process measures and compared VISN 1 sites with 116 VA sites located outside VISN 1. RESULTS: VISN 1 sites improved on TTR, our main indicator of quality, from 66.4% to 69.2%, whereas sites outside VISN 1 improved from 65.9% to 66.4% (DID 2.3%, P < 0.001). Improvement in TTR correlated strongly with the extent of improvement on process-of-care measures, which varied widely across VISN 1 sites. CONCLUSIONS: A regional quality improvement initiative, using performance measurement with audit and feedback, improved TTR by 2.3% more than control sites, which is a clinically important difference. Improving relevant processes of care can improve outcomes for patients receiving warfarin.

Bariatric Surgery -A Viable Option and the Best Hope for Many Mississippians?

[Research shows that diets are ineffective in the treatment of obesity because neuro-hormonal systems to preserve excess weight are stronger than the will to keep it off No magic pill has worked or is on the horizon. Newel; minimally invasive bariatricsurgery procedures do work but may be underutilized. In this Commentaiy, the authors who are affiliated with the UMMC Mississippi Centerfor Obesity Research and one of whom trained at the London School of Economics (ELW), speak to this issue. ---Ed.].

Effect of race and histology on patterns of failure in women with early stage endometrial cancer treated with high dose rate brachytherapy.

BACKGROUND: Clinical trials have helped refine management of early stage endometrial cancer (EC). For patients with intermediate risk features, adjuvant radiation is considered, primarily vaginal cuff brachytherapy. For higher risk patients, there may be a role for chemotherapy and radiation. The purpose of this study is to examine patterns of failure for early stage EC patients treated with postoperative high dose rate brachytherapy. METHODS: In this single institution retrospective cohort study, 208 women with early stage endometrial cancer who received definitive therapy between January 1, 2000 and January 1, 2013 were identified. RESULTS: Median follow-up was 46.4 (range, 6.2-137.3) months. Thirteen (6.3%) patients developed with locoregional recurrent disease and 15 (7.2%) patients developed distant metastasis. Freedom from recurrence at 5 years was 88.6% for white patients and 60.5% for black patients (p=0.0093). Five year recurrence free survival (RFS) for white vs. black patients was 82.9% vs. 48.9% (p=0.0007). Five year overall survival (OS) was 86.8% for white patients and 59.5% for black patients (p=0.0023). Black patients with unfavorable histology treated with chemotherapy and vaginal brachytherapy had a 15% locoregional recurrence rate, more than double the rate of local recurrence compared to AA patients with endometrioid histology and white patients with any histology (6% locoregional recurrence rate). CONCLUSIONS: Black women with unfavorable histology early stage EC experience increased rates of recurrence and worse survival compared to white patients. Patterns of failure in this group also indicate a high locoregional failure rate for the black patients with unfavorable histology (type II).

Evaluating a train-the-trainer approach for improving capacity for evidence-based decision making in public health.

BACKGROUND: Evidence-based public health gives public health practitioners the tools they need to make choices based on the best and most current evidence. An evidence-based public health training course developed in 1997 by the Prevention Research Center in St. Louis has been taught by a transdisciplinary team multiple times with positive results. In order to scale up evidence-based practices, a train-the-trainer initiative was launched in 2010. METHODS: This study examines the outcomes achieved among participants of courses led by trained state-level faculty. Participants from trainee-led courses in four states (Indiana, Colorado, Nebraska, and Kansas) over three years were asked to complete an online survey. Attempts were made to contact 317 past participants. One-hundred forty-four (50.9 %) reachable participants were included in analysis. Outcomes measured include frequency of use of materials, resources, and other skills or tools from the course; reasons for not using the materials and resources; and benefits from attending the course. Survey responses were tabulated and compared using Chi-square tests. RESULTS: Among the most commonly reported benefits, 88 % of respondents agreed that they acquired knowledge about a new subject, 85 % saw applications for the knowledge to their work, and 78 % agreed the course also improved abilities to make scientifically informed decisions at work. The most commonly reported reasons for not using course content as much as intended included not having enough time to implement evidence-based approaches (42 %); other staff/peers lack training (34 %); and not enough funding for continued training (34 %). The study findings suggest that utilization of course materials and teachings remains relatively high across practitioner groups, whether they were taught by the original trainers or by state-based trainers. CONCLUSIONS: The findings of this study suggest that train-the-trainer is an effective method for broadly disseminating evidence-based public health principles. Train-the-trainer is less costly than the traditional method and allows for courses to be tailored to local issues, thus making it a viable approach to dissemination and scale up of new public health practices.

Dosimetric effect due to the motion during deep inspiration breath hold for left-sided breast cancer radiotherapy.

Deep inspiration breath-hold (DIBH) radiotherapy for left-sided breast cancer can reduce cardiac exposure and internal motion. We modified our in-house treatment planning system (TPS) to retrospectively analyze breath-hold motion log files to calculate the dosimetric effect of the motion during breath hold. Thirty left-sided supine DIBH breast patients treated using AlignRT were studied. Breath-hold motion was recorded ­ three translational and three rotational displacements of the treatment surface ­ the Real Time Deltas (RTD). The corresponding delivered dose was estimated using the beam-on portions of the RTDs. Each motion was used to calculate dose, and the final estimated dose was the equally weighted average of the multiple resultant doses. Ten of thirty patients had internal mammary nodes (IMN) purposefully included in the tangential fields, and we evaluated the percentage of IMN covered by 40 Gy. The planned and delivered heart mean dose, lungs V20 (volume of the lungs receiving > 20 Gy), percentage of IMN covered by 40 Gy, and IMN mean dose were compared. The averaged mean and standard deviation of the beam-on portions of the absolute RTDs were 0.81 ± 1.29 mm, 0.68 ± 0.85mm, 0.76 ± 0.85 mm, 0.96° ± 0.49°, 0.93° ± 0.43°, and 1.03° ± 0.50°, for vertical, longitudinal, lateral, yaw, roll, and pitch, respectively. The averaged planned and delivered mean heart dose were 99 and 101 cGy. Lungs V20 were 6.59% and 6.74%. IMN 40 Gy coverage was 83% and 77%, and mean IMN dose was 4642 and 4518 cGy. The averaged mean motion during DIBH was smaller than 1 mm and 1°, which reflects the relative reproducibility of the patient breath hold. On average, the mean heart dose and lungs V20 were reasonably close to what have been planned. IMN 40 Gy coverage might be modestly reduced for certain cases.

Hypofractionation for breast cancer: lessons learned from our neighbors to the north and across the pond.

Adjuvant whole breast irradiation was established within the standard of care for breast-conserving therapy in the early 1980s, following the results of major randomized trials comparing mastectomy vs breast-conserving surgery and radiation. Since that time, techniques and treatment strategies have evolved, but one major thread that carries forward is the need to balance cost, efficacy, complications, and convenience. Fortunately, data from randomized trials conducted in Canada and Great Britain provide a solid framework for the consideration of hypofractionated radiation in the treatment of breast cancer. In this review we discuss the rationale and underlying radiobiologic concepts for hypofractionation, and review the clinical trials and American Society for Radiation Oncology (ASTRO) guidelines supporting this approach. We also review the practical considerations for treatment planning, including dosimetric criteria and how to approach treatment of the node-positive patient. In the current era of healthcare reform and cost awareness, thoughtful utilization of hypofractionation may offer considerable savings to individual patients and the healthcare system--without compromising clinical outcomes or quality of life.

Health care system collaboration to address chronic diseases: a nationwide snapshot from state public health practitioners.

INTRODUCTION: Until recently, health care systems in the United States often lacked a unified approach to prevent and manage chronic disease. Recent efforts have been made to close this gap through various calls for increased collaboration between public health and health care systems to better coordinate provision of services and programs. Currently, the extent to which the public health workforce has responded is relatively unknown. The objective of this study is to explore health care system collaboration efforts and activities among a population-based sample of state public health practitioners. METHODS: During spring 2013, a national survey was administered to state-level chronic disease public health practitioners. Respondents were asked to indicate whether or not they collaborate with health care systems. Those who reported "yes" were asked to indicate all topic areas in which they collaborate and provide qualitative examples of their collaborative work. RESULTS: A total of 759 respondents (84%) reported collaboration. Common topics of collaboration activities were tobacco, cardiovascular health, and cancer screening. More client-oriented interventions than system-wide interventions were found in the qualitative examples provided. Respondents who collaborated were also more likely to use the Community Guide, use evidence-based decision making, and work in program areas that involved secondary, rather than primary, prevention. CONCLUSION: The study findings indicate a need for greater guidance on collaboration efforts that involve system-wide and cross-system interventions. Tools such as the Community Guide and evidence-based training courses may be useful in providing such guidance.

Perceived benefits and challenges of coordinated approaches to chronic disease prevention in state health departments.

INTRODUCTION: Chronic disease prevention efforts have historically been funded categorically according to disease or risk factor. Federal agencies are now progressively starting to fund combined programs to address common risk. The purpose of this study was to inform transitions to coordinated chronic disease prevention by learning views on perceived benefits and challenges of a coordinated approach to funding. METHODS: A national survey on evidence-based public health was conducted from March through May 2013 among state health department employees working in chronic disease prevention (N = 865). Participants were asked to rank the top 3 benefits and top 3 challenges in coordinating chronic disease approaches from provided lists and could provide additional responses. Descriptive analyses, χ(2) tests, and analysis of variance were conducted. RESULTS: The most common perceived benefits of coordinated approaches to chronic disease prevention were improved health outcomes, common risk factors better addressed, and reduced duplication of program efforts. The most common perceived challenges were funding restrictions, such as disease-specific performance measures; competing priorities; lack of communication across programs; funding might be reduced; agency not structured for program coordination; and loss of disease-specific partner support. Rankings of benefits and challenges were similar across states and participant roles; the perceived challenges "lack of communication across programs" (P = .02) and "funding might be reduced" differed by program area (P < .001). CONCLUSION: Findings can be used by funding agencies and state health departments for planning, training, and technical assistance. The information on perceived challenges demonstrates the need to improve communication across programs, enhance organizational support for coordinated approaches, and create benefits for organizational partners.

Breast cancer in Mississippi: impact of race and residential geographical setting on cancer at initial diagnosis.

OBJECTIVE: To analyze female breast cancer data for Mississippi from 2005 to 2009 to test whether race and/or geography had an impact on the stage of breast cancer at the time of diagnosis. METHODS: A cross-sectional design for data was developed and collected by the Mississippi Cancer Registry (MCR). The MCR dataset contained female breast cancer cases diagnosed between 2005 and 2009. Of the 9699 cases used, 2925 were white patients living in urban counties and 3584 were white patients residing in a rural county. Among African American patients, 1247 lived in urban areas, and 1943 resided in rural counties. RESULTS: Geography had a significant impact on the stage of breast cancer at which the patient was diagnosed. Women living in rural Mississippi had a greater chance (white 4% and African American 19%) of presenting with advanced regional/distant breast cancer rather than in situ/localized breast cancer. The number of white patients was similar to the number of African American patients who presented at the time of diagnosis with advanced regional/distant breast cancer. African American women had greater odds than white women (urban 25%, rural 47%) of presenting with advanced regional/distant breast cancer. CONCLUSIONS: This study provides important new information about two specific factors that may affect the stage of breast cancer diagnosis: race (whites vs African Americans) and geography (urban vs rural county). The implications of this study will aid the Mississippi State Department of Health in targeting screening programs throughout the state. The results also may affect medical and allied health care.

Phase 2 study of pre-excision single-dose intraoperative radiation therapy for early-stage breast cancers: six-year update with application of the ASTRO accelerated partial breast irradiation consensus statement criteria.

BACKGROUND: Intraoperative radiation therapy (IORT) allows delivery of high-dose radiation at the time of lumpectomy, potentially sparing adjuvant daily radiation. A phase 2 study of pre-excision IORT was performed for early-stage breast cancer. METHODS: Patients ≥ 48 years of age with invasive ductal carcinoma, ≤ 3 cm, and clinically node-negative were eligible for this study, which was approved by institutional review board. Ultrasound was used to select electron energy and cone size to cover the tumor plus 1.5- to 2.0-cm lateral margins and 1-cm-deep margins (90% isodose). Fifteen Gy was delivered with a Mobetron irradiator, and immediate needle-localized partial mastectomy followed. Local event results were updated using the Kaplan-Meier method. RESULTS: A total of 53 patients received IORT alone. Median age was 63 years, and median tumor size was 1.2 cm. Of these, 81% were positive for estrogen receptor or progesterone receptor, 11% were positive for human epidermal growth factor receptor 2, and 15% were triple-negative. Also, 42%, 49%, and 9% would have fallen into the Suitable, Cautionary, and Unsuitable groups, respectively, of the American Society of Therapeutic Radiation Oncology consensus statement for accelerated partial breast irradiation. Median follow-up was 69 months. Ipsilateral events occurred in 8 of 53 patients. The 6-year actuarial rate of ipsilateral events was 15% (95% confidence interval = 7%-29%). The crude event rate for Suitable and Cautionary groups was 1 of 22 (5%) and 7 of 26 (27%), respectively. Overall survival was 94.4%, and breast cancer-specific survival was 100%. CONCLUSIONS: The rate of local events in this study is a matter of concern, especially in the Cautionary group. On the basis of these findings, pre-excision IORT, as delivered in this study, may not provide adequate local control for less favorable early-stage breast cancers.

Strategic priorities to increase use of clinical preventive services among older US adults.

The objective of this project was to obtain professionals' perceptions of system-level strategies with potential to increase use of clinical preventive services (CPS) among adults aged 50 years or older through community settings. Public health, aging services, and medical professionals participated in guided discussions and a modified Delphi process. Priority strategies, determined on the basis of a 70% or higher a priori agreement level, included enhancing community capacity; promoting the design of health information technologies to exchange data between clinical and community settings; promoting care coordination; broadening scope of practice; providing incentives to employers; and eliminating cost-sharing. Findings provide insights about preferences for system-level strategies that align with national and state initiatives to increase CPS use.