On the influence of test speed and environment in the fatigue life of small diameter nitinol and stainless steel wire.

To better understand the complex interplay of speed and environment on metals commonly used in implants, rotary bend fatigue tests were conducted on stainless steel and nitinol wires. A range of alternating strains was tested to create ε-N curves at two speeds (physiologic and accelerated) and in three environments (deionized water at body temperature, phosphate buffered saline at body temperature, and laboratory air at ambient room temperature). Results indicate that speed and environment can affect the observed fatigue life in nuanced ways. An electropotential monitoring technique was demonstrated to characterize fatigue crack growth which may be useful in future investigations.

Longitudinal tracking of 97 esophageal adenocarcinomas using liquid biopsy sampling.

BACKGROUND: The incidence of esophageal adenocarcinoma (EAC) is rapidly rising and has a 5-year survival rate of <20%. Beyond TNM (tumor-node-metastasis) staging, no reliable risk stratification tools exist and no large-scale studies have profiled circulating tumor DNA (ctDNA) at relapse in EAC. Here we analyze the prognostic potential of ctDNA dynamics in EAC, taking into account clonal hematopoiesis with indeterminate potential (CHIP). PATIENTS AND METHODS: A total of 245 samples from 97 patients treated with neoadjuvant chemotherapy and surgery were identified from the prospective national UK Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) consortium data set. A pan-cancer ctDNA panel comprising 77 genes was used. Plasma and peripheral blood cell samples were sequenced to a mean depth of 7082× (range 2196-28 524) and ctDNA results correlated with survival. RESULTS: Characteristics of the 97 patients identified were as follows: 83/97 (86%) male, median age 68 years (SD 9.5 years), 100% cT3/T4, 75% cN+. EAC-specific drivers had higher variant allele fractions than passenger mutations. Using stringent quality criteria 16/79 (20%) were ctDNA positive following resection; recurrence was observed in 12/16 (75%) of these. As much as 78/97 (80%) had CHIP analyses that enabled filtering for CHIP variants, which were found in 18/78 (23%) of cases. When CHIP was excluded, 10/63 (16%) patients were ctDNA positive and 9/10 of these (90%) recurred. With correction for CHIP, median cancer-specific survival for ctDNA-positive patients was 10.0 months versus 29.9 months for ctDNA-negative patients (hazard ratio 5.55, 95% confidence interval 2.42-12.71; P = 0.0003). Similar outcomes were observed for disease-free survival. CONCLUSIONS: We demonstrate in a large, national, prospectively collected data set that ctDNA in plasma following surgery for EAC is prognostic for relapse. Inclusion of peripheral blood cell samples can reduce or eliminate false positives from CHIP. In future, post-operative ctDNA could be used to risk stratify patients into high- and low-risk groups for intensification or de-escalation of adjuvant chemotherapy.

Direct drive with the argon fluoride laser as a path to high fusion gain with sub-megajoule laser energy.

Argon fluoride (ArF) is currently the shortest wavelength laser that can credibly scale to the energy and power required for high gain inertial fusion. ArF's deep ultraviolet light and capability to provide much wider bandwidth than other contemporary inertial confinement fusion (ICF) laser drivers would drastically improve the laser target coupling efficiency and enable substantially higher pressures to drive an implosion. Our radiation hydrodynamics simulations indicate gains greater than 100 are feasible with a sub-megajoule ArF driver. Our laser kinetics simulations indicate that the electron beam-pumped ArF laser can have intrinsic efficiencies of more than 16%, versus about 12% for the next most efficient krypton fluoride excimer laser. We expect at least 10% 'wall plug' efficiency for delivering ArF light to target should be achievable using solid-state pulsed power and efficient electron beam transport to the laser gas that was demonstrated with the U.S. Naval Research Laboratory's Electra facility. These advantages could enable the development of modest size and lower cost fusion power plant modules. This would drastically change the present view on inertial fusion energy as being too expensive and the power plant size too large. This article is part of a discussion meeting issue 'Prospects for high gain inertial fusion energy (part 1)'.

Molecular chemisorption of N2 on IrO2(110).

We investigated adsorption of N2 on stoichiometric and O-rich IrO2(110) surfaces using temperature programmed desorption (TPD) experiments and density functional theory (DFT) calculations. TPD shows that N2 desorbs predominantly from the stoichiometric-IrO2(110) surface in a well-defined peak at 270 K for N2 coverages below about 0.5 ML and that a shoulder centered near 235 K develops in the N2 TPD traces as the coverage approaches saturation, indicating that adsorbed N2 molecules destabilize at high N2 coverages. Experiments of N2 adsorption onto O-rich IrO2(110) surfaces provide evidence that N2 adsorbs exclusively on the coordinatively unsaturated Ir atoms (Ircus) of the surface and that pre-adsorbed O-atoms ("on-top" oxygen) stabilize adsorbed N2 molecules, causing the main N2 TPD peak to shift toward higher temperature with increasing oxygen coverages. Consistent with prior results, our DFT calculations predict that an N2 molecule preferentially adsorbs into an upright configuration on an Ircus atom of the IrO2(110) surface and achieves a binding energy of about 100 kJ/mol. The computed binding energy agrees well with our experimental estimate of ∼90 kJ/mol for low N2 coverages on stoichiometric IrO2(110). The DFT calculations also quantitatively reproduce the observed stabilization of N2 by co-adsorption on-top O-atoms and predict the destabilization of N2 on IrO2(110) as the N2 adlayer becomes crowded at high coverages.

Estimating within-flock transmission rate parameter for H5N2 highly pathogenic avian influenza virus in Minnesota turkey flocks during the 2015 epizootic.

Better control of highly pathogenic avian influenza (HPAI) outbreaks requires deeper understanding of within-flock virus transmission dynamics. For such fatal diseases, daily mortality provides a proxy for disease incidence. We used the daily mortality data collected during the 2015 H5N2 HPAI outbreak in Minnesota turkey flocks to estimate the within-flock transmission rate parameter (ß). The number of birds in Susceptible, Exposed, Infectious and Recovered compartments was inferred from the data and used in a generalised linear mixed model (GLMM) to estimate the parameters. Novel here was the correction of these data for normal mortality before use in the fitting process. We also used mortality threshold to determine HPAI-like mortality to improve the accuracy of estimates from the back-calculation approach. The estimated ß was 3.2 (95% confidence interval (CI) 2.3-4.3) per day with a basic reproduction number of 12.8 (95% CI 9.2-17.2). Although flock-level estimates varied, the overall estimate was comparable to those from other studies. Sensitivity analyses demonstrated that the estimated ß was highly sensitive to the bird-level latent period, emphasizing the need for its precise estimation. In all, for fatal poultry diseases, the back-calculation approach provides a computationally efficient means to obtain reasonable transmission parameter estimates from mortality data.

Performance of Veterinary Services Pathway evolution and One Health aspects.

Animals, and the health systems which ensure their protection, play a vital role in the security and economic and social well-being of humanity, and are therefore a key component of the One Health concept. For global and national health security, prevention is better than cure, and targeting 'risk at source' in animal populations is a vital strategy in safeguarding the planet from risks of emerging zoonoses and antimicrobial resistance (AMR). Neglected zoonoses - such as rabies and brucellosis - continue to have a significant global impact on human health and are also best managed at their animal source. The World Organisation for Animal Health (OIE) has built international consensus on the principles of good governance and the quality of Veterinary Services, which are incorporated within its international standards. The OIE has a proven track record in the provision of Member Country support based on these standards, especially since the advent of its flagship Performance of Veterinary Services (PVS) Pathway programme in 2006-2007. To date, approximately 140 countries have benefited from the structured and sustainable process of animal health systems evaluation and planning afforded by the PVS Pathway. The PVS Tool, the basic methodology upon which the PVS Pathway is based, addresses One Health by evaluating the Veterinary Authority's ability to coordinate with other Competent Authorities that have a role to play in One Health, most notably public health, food safety, and environmental authorities. Despite the undoubted success of the PVS Pathway, the OIE felt that it was time to consider how the programme might be developed to adapt to new challenges. Consequently, during 2017-2018, the OIE embarked on a process of PVS evolution, during which it carried out extensive consultation and further tailored the PVS Pathway to a changing global context. These improvements, which include both fundamental adaptations to the PVS Pathway methods and the development of new PVS Pathway activities targeting topics such as multisectoral collaboration, rabies and AMR, have further strengthened and embedded the One Health approach within the PVS Pathway.

Parce qu'ils jouent un rôle crucial pour la sécurité et le bien-être économique et social de l'humanité, les animaux et les systèmes sanitaires en charge de leur protection sont une composante clé du concept Une seule santé. En matière de sécurité sanitaire à l'échelle du monde ou d'un pays, il vaut toujours mieux prévenir que guérir ; c'est pourquoi la stratégie consistant à cibler le risque à sa source est la seule qui puisse protéger la planète contre les zoonoses émergentes et le développement de l'antibiorésistance. L'impact sur la santé publique des zoonoses négligées comme la rage et la brucellose reste important et c'est également à leur source animale que les interventions visant à les contrôler sont les plus efficaces. L'Organisation mondiale de la santé animale (OIE) a forgé un consensus international autour des principes de bonne gouvernance et de qualité des Services vétérinaires et les a inscrites au coeur de ses normes internationales. L'OIE a démontré sa capacité à apporter aux Pays membres un soutien basé sur ces normes, en particulier depuis la création en 2006­2007 du Processus sur les Performances des Services vétérinaires (PVS), son programme phare. À ce jour, près de 140 pays ont bénéficié d'une procédure structurée d'évaluation et de planification durable de leurs systèmes de santé animale, grâce au Processus PVS. L'Outil PVS, instrument méthodologique du Processus PVS, couvre certains aspects relevant de l'approche Une seule santé en évaluant les capacités de concertation des Autorités vétérinaires avec d'autres autorités compétentes ayant un rôle à jouer dans ce contexte, en particulier celles en charge de la santé publique, de la sécurité sanitaire des aliments et de la protection de l'environnement. En dépit de la réussite incontestée du Processus PVS, l'OIE a estimé que le temps était venu d'envisager l'évolution de ce programme afin de l'adapter aux nouveaux défis. En conséquence, l'OIE a lancé en 2017­2018 la phase d'Évolution du Processus OIE à travers de larges consultations visant à adapter le Processus PVS aux mutations du contexte mondial. Les améliorations apportées, qui portent à la fois sur les fondements méthodologiques et sur la conception de nouvelles activités du Processus PVS dédiées à des sujets tels que la collaboration multisectorielle, la rage et la résistance aux agents antimicrobiens ont renforcé l'approche Une seule santé ainsi que son ancrage dans le Processus PVS.

Los animales y los sistemas sanitarios que velan por su protección cumplen una función vital para la seguridad y el bienestar económico y social de la humanidad, razón por la cual constituyen un elemento básico del concepto de Una sola salud. Desde el punto de vista de la seguridad sanitaria del mundo y de los países, más vale prevenir que curar, y el hecho de ir a combatir un riesgo en las poblaciones animales en las que tiene su origen es una estrategia indispensable para salvaguardar al planeta de los peligros que entrañan las zoonosis emergentes y la resistencia a los antimicrobianos. La mejor forma de luchar contra zoonosis desatendidas como la rabia o la brucelosis, que en todo el mundo siguen repercutiendo sensiblemente en la salud humana, pasa por atacarlas en su origen animal. La Organización Mundial de Sanidad Animal (OIE) ha sabido suscitar un consenso internacional en torno a los principios de buen gobierno y calidad de los Servicios Veterinarios, integrados ahora en sus normas internacionales. La OIE goza de contrastada experiencia en la prestación de apoyo a los Países Miembros basándose en estas normas, especialmente desde la instauración en 2006­2007 de su emblemático programa llamado Proceso PVS (Prestaciones de los Servicios Veterinarios). Hasta la fecha, alrededor de 140 países han podido beneficiarse del procedimiento estructurado y sostenible de evaluación y planificación de los sistemas de sanidad animal que se propone a través del Proceso PVS. La Herramienta PVS aporta la metodología básica en que descansa el Proceso PVS: con ella se trabaja en clave de Una sola salud evaluando la capacidad de la Autoridad Veterinaria del país para coordinarse con las demás autoridades competentes que cumplen alguna función relacionada con Una sola salud, sobre todo las de salud pública, seguridad sanitaria de los alimentos y medio ambiente. Pese al indiscutible éxito cosechado por el Proceso PVS, la OIE estimó llegado el momento de plantearse hacia dónde hacer evolucionar el programa para adaptarlo a nuevas problemáticas. Obrando en consecuencia, en 2017 y 2018 la OIE se embarcó en un proceso de «evolución del PVS¼ durante el cual celebró vastas consultas y adaptó aún más el Proceso PVS a un panorama mundial en constante evolución, incorporándole mejoras que incluyen a la vez una serie de ajustes básicos en los métodos del Proceso PVS y la creación de nuevas actividades encuadradas en él sobre temas como la colaboración multisectorial, la rabia o la resistencia a los antimicrobianos, mejoras que a la postre han servido para potenciar la filosofía de Una sola salud e integrarla aún más en el Proceso PVS.

The impact of GI events on persistence and adherence to osteoporosis treatment: 3-, 6-, and 12-month findings in the MUSIC-OS study.

The goal of this multinational, prospective, observational study was to examine the relationship between gastrointestinal (GI) events and self-reported levels of medication adherence and persistence in postmenopausal women. A total of 73.9% of patients remained on their osteoporosis (OP) therapy at month 12, although the presence of a GI event at baseline, month 3, and month 6 significantly reduced month 12 persistence among new users. The odds of a month-12 ADEOS score ≥ 20 were significantly lower among patients who experienced a GI event between baseline and month 6. The occurrence of GI events was observed to be associated with a lower likelihood of patient adherence and persistence to OP medication. INTRODUCTION: This study examines the relationship between gastrointestinal (GI) events and self-reported adherence and persistence with initial osteoporosis (OP) therapy over the course of the first 12 months of treatment. METHODS: The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study was a multinational, prospective, observational study examining the impact of GI events on OP management in postmenopausal women. Information regarding GI events was collected at the time of enrollment and at months 3, 6, and 12 of follow-up. Patients reported GI events and medication persistence and completed the 12-item Adherence Evaluation of Osteoporosis treatment (ADEOS) questionnaire. Multivariate logistic and general linear models examined the association between GI events at various time points and persistence and adherence at month 12. RESULTS: The study enrolled 2943 women; 22.8% were classified as new users of OP therapy and the remainder were considered experienced users. Across all patients, 68.1% reported GI events at baseline; by month 12, over 80% of subjects who completed follow-up reported at least one GI problem. The majority of patients (86.7%) were treated only with bisphosphonates at baseline. At month 12, 73.9% of patients remained on therapy; logistic regression revealed that those with GI problems by month 6 were significantly less likely to persist with treatment, after adjusting for other factors. The odds of a month 12 ADEOS score ≥ 20 (considered predictive of adherence) were significantly lower among patients who experienced a GI event between baseline and month 6. CONCLUSIONS: The occurrence of GI events was associated with a lower likelihood of patient adherence to and persistence with OP medication.

Portrayal of Brain Death in Film and Television.

We sought to evaluate whether television and cinematic coverage of brain death is educational or misleading. We identified 24 accessible productions that addressed brain death using the archives of the Paley Center for Media (160 000 titles) and the Internet Movie Database (3.7 million titles). Productions were reviewed by two board-certified neurologists. Although 19 characters were pronounced brain dead, no productions demonstrated a complete examination to assess for brain death (6 included an assessment for coma, 9 included an evaluation of at least 1 brainstem reflex, but none included an assessment of every brainstem reflex, and 2 included an apnea test). Subjectively, both authors believed only a small fraction of productions (13% A.L., 13% J.W.) provided the public a complete and accurate understanding of brain death. Organ donation was addressed in 17 productions (71%), but both reviewers felt that the discussions about organ donation were professional in a paucity of productions (9% for A.L., 27% for J.W.). Because television and movies serve as a key source for public education, the quality of productions that feature brain death must be improved.

Frequency of discontinuation of injectable osteoporosis therapies in US patients over 2 years.

Little is known about treatment patterns with injectable osteoporosis therapies. At 12 months, the probability of discontinuation was 69.1% among patients using ibandronate, followed by teriparatide (67.1%), zoledronic acid (59.2%), and denosumab (48.8%). By 24 months, discontinuation was higher for each treatment. The majority of US patients discontinue injectable osteoporosis treatment by the end of the first year following initiation. INTRODUCTION: This study was designed to assess the frequency of treatment discontinuation over time among patients who initiate injectable osteoporosis therapies. METHODS: This retrospective observational study utilized an administrative claims database to measure discontinuation of injectable osteoporosis therapy, reported at 6-month intervals over 2 years. Eligible patients were aged ≥55 years, had newly initiated injectable osteoporosis therapy between January 2008 and June 2012, and were continuously enrolled in the health plan for ≥1 year prior to and ≥1.5 years after the date the first injectable medication was received (the index date). Follow-up time ranged from 18 to 24 months. Injectable osteoporosis treatments included in the analysis were denosumab, ibandronate, teriparatide, and zoledronic acid. Discontinuation was assessed using Kaplan-Meier survival analysis and was defined at each time point as the percentage of patients who did not receive the dose scheduled for that time point. A 90-day grace period was allowed to accommodate flexibility in the scheduling of post-index re-administrations. Sensitivity analyses assessed discontinuation using grace periods of 60 and 30 days. RESULTS: A total of 4756 patients met the inclusion criteria for the study, with 617 utilizing denosumab, 233 ibandronate, 778 teriparatide, and 3128 zoledronic acid. At 12 months, discontinuation was highest among patients using ibandronate (69.1%), followed by teriparatide (67.1%), zoledronic acid (59.2%), and denosumab (48.8%). By 24 months, discontinuation was higher for each treatment: 87.5% for ibandronate, 87.9% for teriparatide, 79.8% for zoledronic acid, and 64.3% for denosumab. CONCLUSIONS: The majority of US patients discontinue injectable osteoporosis treatment by the end of the first year following initiation.

Association of gastrointestinal events with quality of life and treatment satisfaction in osteoporosis patients: results from the Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study (MUSIC OS).

The purpose of this study was to assess the association of GI events with HRQoL and treatment satisfaction. The effect of baseline GI events persisted through 1 year of follow-up, as indicated by lower EQ-5D, OPAQ-SV, and treatment satisfaction scores among patients with vs without baseline GI events. The presence of GI events is an independent predictor of decreased HRQoL and treatment satisfaction in patients being treated for osteoporosis. INTRODUCTION: The goal of this study was to assess the association of gastrointestinal (GI) events with health-related quality of life (HRQoL) and treatment satisfaction in patients being treated for osteoporosis. METHODS: MUSIC OS was a multinational, prospective, observational study examining the impact of GI events on osteoporosis management in postmenopausal women. In this analysis, HRQoL and treatment satisfaction were assessed at baseline, 6, and 12 months and compared between patients with and without GI events. Covariate-adjusted scores were calculated using multivariate least-squares regression analysis, and differences between the mean scores of patients with and without baseline and post-baseline GI events were determined. RESULTS: Among the 2959 patients in the analysis, unadjusted scores at each time point were lower (i.e., worse) for patients with GI events than patients without GI events. In adjusted analyses, the effect of baseline GI events persisted through 1 year of follow-up, as indicated by lower EQ-5D and OPAQ-SV scores at 12 months among patients with vs without baseline GI events (-0.04 for the EQ-5D utility score, -5.07 for the EQ-5D visual analog scale, -3.35 for OPAQ physical function, -4.60 for OPAQ emotional status, and -8.50 for OPAQ back pain; P ≤ 0.001 for all values). Decrements in month 12 treatment satisfaction scores were -6.46 for patients with baseline GI events and -7.88 for patients with post-baseline GI events. CONCLUSIONS: The presence of GI events is an independent predictor of decreased HRQoL and treatment satisfaction in patients being treated for osteoporosis.

Disparities in osteoporosis treatments.

UNLABELLED: Osteoporosis treatment rates within 2 years following an index event (fragility fracture, osteoporotic bone mineral density (BMD) T-score, or osteoporosis ICD-9 codes) were determined from 2005 to 2011. Most patients were not treated. Fracture patients had the lowest treatment rate. Low treatment rates also occurred in patients that were male, black, or had non-commercial insurance. INTRODUCTION: Clinical recognition of osteoporosis (osteoporotic BMD, assignment of an ICD-9 code, or the occurrence of fragility fractures) provides opportunities to treat patients at risk for future fracture. METHODS: A cohort of 36,965 patients was identified from 2005 to 2011 in the Indiana Health Information Exchange, with index events after age 50 of either non-traumatic fractures, an osteoporosis ICD-9 code, or a BMD T-score ≤ -2.5. Patients with osteoporosis treatment in the preceding year were excluded. Medication records during the ensuing 2 years were extracted to identify osteoporosis treatments, demographics, comorbidities, and co-medications. Predictors of treatment were evaluated in a multivariable logistic regression model. RESULTS: The cohort was 78 % female, 11 % black, 91 % urban-dwelling, and 53 % commercially insured. The index events were as follows: osteoporosis diagnosis (47 % of patients), fragility fracture (44 %), and osteoporotic T-scores (9 %). Within 2 years after the index event, 23.3 % received osteoporosis medications (of which, 82.2 % were oral bisphosphonates). Treatment rates were higher after osteoporosis diagnosis codes (29.3 %) or osteoporotic T-score (53.9 %) than after fracture index events (10.5 %) (p < 0.001). Age had an inverted U-shaped effect for women with highest odds around 60-65 years. Women (OR 1.86) and non-black patients (OR 1.52) were more likely to be treated (p < 0.001). Patients with public (versus commercial) insurance (OR 0.86, p < 0.001) or chronic comorbidities (ORs about 0.7-0.9, p < 0.001) were less likely to be treated. CONCLUSION: Most osteoporosis treatment candidates remained untreated. Men, black patients, and patients with fracture or chronic comorbidities were less likely to receive treatment, representing disparity in the recognition and treatment of osteoporosis.

Gastrointestinal symptoms and association with medication use patterns, adherence, treatment satisfaction, quality of life, and resource use in osteoporosis: baseline results of the MUSIC-OS study.

SUMMARY: The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study (MUSIC-OS) is a prospective, observational study of women with osteoporosis in Europe and Canada. At baseline, patients with gastrointestinal symptoms reported lower adherence to osteoporosis treatment, treatment satisfaction, and health-related quality of life, than those without gastrointestinal symptoms. INTRODUCTION: The aim of the study was to examine gastrointestinal (GI) symptoms and the association between GI symptoms and treatment adherence, treatment satisfaction, and health-related quality of life (HRQoL) among osteoporotic women in Europe and Canada. METHODS: Baseline results are reported here for a prospective study which enrolled postmenopausal, osteoporotic women who were initiating (new users) or continuing (experienced users) osteoporosis treatment at study entry (baseline). A patient survey was administered at baseline and included the occurrence of GI symptoms during 6-month pre-enrolment, treatment adherence (adherence evaluation of osteoporosis (ADEOS), score 0-22), treatment satisfaction (Osteoporosis Treatment Satisfaction Questionnaire for Medications (OPSAT-Q), score 0-100) and HRQoL (EuroQol-5 dimension (EQ-5D) utility, score 0-1; OPAQ-SV, score 0-100). The association between GI symptoms and ADEOS (experienced users), OPSAT-Q (experienced users), and HRQoL (new and experienced users) was assessed by general linear models adjusted for patient characteristics. RESULTS: A total of 2959 patients (2275 experienced and 684 new users) were included. Overall, 68.1% of patients experienced GI symptoms in the past 6 months. Compared with patients without GI symptoms, patients with GI symptoms had lower mean baseline scores on most measures. The mean adjusted differences were ADEOS, -0.43; OPSAT-Q, -5.68; EQ-5D, -0.04 (new users) and -0.06 (experienced users), all P < 0.01. GI symptoms were also associated with lower OPAQ-SV domain scores: physical function, -4.17 (experienced users); emotional status, -4.28 (new users) and -5.68 (experienced users); back pain, -5.82 (new users) and -11.33 (experienced users), all P < 0.01. CONCLUSIONS: Patients with GI symptoms have lower treatment adherence and treatment satisfaction and worse HRQoL than patients without GI symptoms.

Suppression of laser nonuniformity imprinting using a thin high-z coating.

Imprinting of laser nonuniformity is a limiting factor in direct-drive inertial confinement fusion experiments, particularly when available laser smoothing is limited. A thin (∼400 Å) high-Z metal coating is found to substantially suppress laser imprint for planar targets driven by pulse shapes and intensities relevant to implosions on the National Ignition Facility while retaining low adiabat target acceleration. A hybrid of indirect and direct drive, this configuration results in initial ablation by x rays from the heated high-Z layer, creating a large standoff for perturbation smoothing.

Clinical significance of patterns of incidental thyroid uptake at (18)F-FDG PET/CT.

Incidental uptake of 2-[(18)F]-fluoro-2-deoxy-d-glucose ((18)F-FDG) in the thyroid gland is not uncommonly encountered in day-to-day practice of oncological (18)F-FDG positron-emission tomography/computed tomography (PET/CT). These are often felt to be "nuisance lesions" by referring clinicians and radiologists alike. However, recognition of the importance of different patterns of FDG uptake in the thyroid gland and knowledge of the possible underlying aetiologies are crucial in ensuring that patients are managed appropriately in the clinical context of their primary diagnosis, as the underlying pathological condition may be clinically important in a significant minority of such cases. This review describes the various patterns of (18)F-FDG uptake within the thyroid and discusses the clinical significance and possible impact on patient management. Incidental low-grade homogeneous diffuse increased thyroid (18)F-FDG uptake is usually seen in the patients with chronic thyroiditis, Grave's disease, and hypothyroidism. Thyroid function tests and antibody profiling are advised in these patients. Incidental focal (18)F-FDG thyroid uptake should raise the possibility of underlying malignancy. Ultrasound with or without fine-needle aspiration cytology is usually recommended for the evaluation of these lesions. Heterogeneous uptake with prominent focal uptake in the thyroid should be further evaluated to exclude malignancy.

Quantitative Estimation of the Number of Contaminated Hatching Eggs Released from an Infected, Undetected Turkey Breeder Hen Flock During a Highly Pathogenic Avian Influenza Outbreak.

The regulatory response to an outbreak of highly pathogenic avian influenza (HPAI) in the United States may involve quarantine and stop movement orders that have the potential to disrupt continuity of operations in the U.S. turkey industry--particularly in the event that an uninfected breeder flock is located within an HPAI Control Area. A group of government-academic-industry leaders developed an approach to minimize the unintended consequences associated with outbreak response, which incorporates HPAI control measures to be implemented prior to moving hatching eggs off of the farm. Quantitative simulation models were used to evaluate the movement of potentially contaminated hatching eggs from a breeder henhouse located in an HPAI Control Area, given that active surveillance testing, elevated biosecurity, and a 2-day on-farm holding period were employed. The risk analysis included scenarios of HPAI viruses differing in characteristics as well as scenarios in which infection resulted from artificial insemination. The mean model-predicted number of internally contaminated hatching eggs released per movement from an HPAI-infected turkey breeder henhouse ranged from 0 to 0.008 under the four scenarios evaluated. The results indicate a 95% chance of no internally contaminated eggs being present per movement from an infected house before detection. Sensitivity analysis indicates that these results are robust to variation in key transmission model parameters within the range of their estimates from available literature. Infectious birds at the time of egg collection are a potential pathway of external contamination for eggs stored and then moved off of the farm; the predicted number of such infectious birds was estimated to be low. To date, there has been no evidence of vertical transmission of HPAI virus or low pathogenic avian influenza virus to day-old poults from hatching eggs originating from infected breeders. The application of risk analysis methods was beneficial for evaluating outbreak measures developed through emergency response planning initiatives that consider the managed movement of hatching eggs from monitored premises in an HPAI Control Area.

Risk Reduction Modeling of High Pathogenicity Avian Influenza Virus Titers in Nonpasteurized Liquid Egg Obtained from Infected but Undetected Chicken Flocks.

Control of highly pathogenic avian influenza (HPAI) outbreaks in poultry has traditionally involved the establishment of disease containment zones, where poultry products are only permitted to move from within a zone under permit. Nonpasteurized liquid egg (NPLE) is one such commodity for which movements may be permitted, considering inactivation of HPAI virus via pasteurization. Active surveillance testing at the flock level, using targeted matrix gene real-time reversed transcriptase-polymerase chain reaction testing (RRT-PCR) has been incorporated into HPAI emergency response plans as the primary on-farm diagnostic test procedure to detect HPAI in poultry and is considered to be a key risk mitigation measure. To inform decisions regarding the potential movement of NPLE to a pasteurization facility, average HPAI virus concentrations in NPLE produced from a HPAI virus infected, but undetected, commercial table-egg-layer flock were estimated for three HPAI virus strains using quantitative simulation models. Pasteurization under newly proposed international design standards (5 log10 reduction) is predicted to inactivate HPAI virus in NPLE to a very low concentration of less than 1 embryo infectious dose (EID)50 /mL, considering the predicted virus titers in NPLE from a table-egg flock under active surveillance. Dilution of HPAI virus from contaminated eggs in eggs from the same flock, and in a 40,000 lb tanker-truck load of NPLE containing eggs from disease-free flocks was also considered. Risk assessment can be useful in the evaluation of commodity-specific risk mitigation measures to facilitate safe trade in animal products from countries experiencing outbreaks of highly transmissible animal diseases.

Effects of non-local exchange on core level shifts for gas-phase and adsorbed molecules.

Density functional theory calculations are often used to interpret experimental shifts in core level binding energies. Calculations based on gradient-corrected (GC) exchange-correlation functionals are known to reproduce measured core level shifts (CLS) of isolated molecules and metal surfaces with reasonable accuracy. In the present study, we discuss a series of examples where the shifts calculated within a GC-functional significantly deviate from the experimental values, namely the CLS of C 1s in ethyl trifluoroacetate, Pd 3d in PdO and the O 1s shift for CO adsorbed on PdO(101). The deviations are traced to effects of the electronic self-interaction error with GC-functionals and substantially better agreements between calculated and measured CLS are obtained when a fraction of exact exchange is used in the exchange-correlation functional.

The association between histopathologic effects and liver weight changes induced in mice and rats by chemical exposures: An analysis of the data from Toxicity Reference Database (ToxRefDB).

Absolute (ALW) and relative (RLW) liver weight changes are sensitive endpoints in repeat-dose rodent toxicity studies, and their changes are often used for quantitative assessment of health effects induced by hepatotoxic chemicals using the benchmark dose-response modeling (BMD) approach. To find biologically relevant liver weight changes to chemical exposures, we evaluated all data available for liver weight changes and associated liver histopathologic findings from the Toxicity Reference Database (ToxRefDB). Our analysis of 389 subchronic mouse and rat studies for 273 chemicals found significant differences in treatment-related ALW and RLW changes between dose groups with and without liver histopathologic changes. In addition, we demonstrate that chemical treatment-induced ALW and RLW changes can predict the presence of histopathologic findings and inform the selection of biologically relevant liver weight changes for BMD modeling and derivation of toxicity values.

Independent transitions to freshwater environments promote phenotypic divergence, not convergence, in stingrays.

Instances of convergent or parallel evolution provide a potent model system for exploring contingency and determinism in evolutionary biology. Likewise, the multiple, independent habitat transitions from saltwater to freshwater biomes offer opportunity for studying convergent evolution within and among different vertebrate lineages. For example, stingrays have invaded freshwater habitats multiple times across different continents, sometimes even several times within the same clade (e.g., Dasyatidae). We evaluated the frequency of saltwater-freshwater invasions in stingrays, compared ecological and phenotypic diversification among freshwater and saltwater lineages, and assessed the degree of convergence among freshwater species. Despite not being morphologically distinct from saltwater stingrays, freshwater stingrays do expand the margins of stingray morphological diversity. According to our data, trophic specialists occupied non-overlapping regions of morphospace, with piscivores and molluscivores being distinct from other diet guilds. Freshwater stingrays as a group did not strongly converge morphologically, neither did freshwater rays from different lineages which shared similar niches. These findings could be explained by there not being enough time for convergence to occur among more ancient and more recent freshwater lineages. Alternatively, the different ancestral bauplans of various freshwater ray lineages and weak selection on optimal phenotypes could promote contingency in the form of evolution along paths of least resistance.