Purpose We ascertained the feasibility and safety of image guided targeted photothermal focal therapy for localized prostate cancer. Materials and Methods Twelve patients with biopsy proven low risk ...prostate cancer underwent interstitial photothermal ablation of the cancer. The area of interest was confirmed and targeted using magnetic resonance imaging. Three-dimensional ultrasound was used to guide a laser to the magnetic resonance to ultrasound fused area of interest. Target ablation was monitored using thermal sensors and real-time Definity® contrast enhanced ultrasound. Followup was performed with a combination of magnetic resonance imaging and prostate biopsy. Validated quality of life questionnaires were used to assess the effect on voiding symptoms and erectile function, and adverse events were solicited and recorded. Results Interstitial photothermal focal therapy was technically feasible to perform. Of the patients 75% were discharged home free from catheter the same day with the remainder discharged home the following day. The treatment created an identifiable hypovascular defect which coincided with the targeted prostatic lesion. There were no perioperative complications and minimal morbidity. All patients who were potent before the procedure maintained potency after the procedure. Continence levels were not compromised. Based on multicore total prostate biopsy at 6 months 67% of patients were free of tumor in the targeted area and 50% were free of disease. Conclusions Image guided focal photothermal ablation of low risk and low volume prostate cancer is feasible. Early clinical, histological and magnetic resonance imaging responses suggest that the targeted region can be ablated with minimal adverse effects. It may represent an alternate treatment approach to observation or delayed standard therapy in carefully selected patients. Further trials are required to demonstrate the effectiveness of this treatment concept.
Ecoregional differences contribute to genetic environmental interactions and impact animal performance. These differences may become more important under climate change scenarios. Utilizing genetic ...diversity within a species to address such problems has not been fully explored. In this study Hereford cattle were genotyped with 50K Bead Chip or 770K Bovine Bead Chip to test the existence of genetic structure in five U.S. ecoregions characterized by precipitation, temperature and humidity and designated: cool arid (CA), cool humid (CH), transition zone (TZ), warm arid (WA), and warm humid (WH). SNP data were analyzed in three sequential analyses. Broad genetic structure was evaluated with STRUCTURE, and ADMIXTURE software using 14,312 SNPs after passing quality control variables. The second analysis was performed using principal coordinate analysis with 66 Tag SNPs associated in the literature with various aspects of environmental stressors (e.g., heat tolerance) or production (e.g., milk production). In the third analysis TreeSelect was used with the 66 SNPs to evaluate if ecoregional allelic frequencies deviated from a central frequency and by so doing are indicative of directional selection. The three analyses suggested subpopulation structures associated with ecoregions from where animals were derived. ADMIXTURE and PCA results illustrated the importance of temperature and humidity and confirm subpopulation assignments. Comparisons of allele frequencies with TreeSelect showed ecoregion differences, in particular the divergence between arid and humid regions. Patterns of genetic variability obtained by medium and high density SNP chips can be used to acclimatize a temperately derived breed to various ecoregions. As climate change becomes an important factor in cattle production, this study should be used as a proof of concept to review future breeding and conservation schemes aimed at adaptation to climatic events.
To examine the association of change in body mass index (BMI) with risk of Alzheimer disease (AD).
Nine hundred eighteen older Catholic clergy participating in the Religious Orders Study without ...dementia at baseline were studied. Outcome measures were the clinical diagnosis of AD and change in cognitive function.
During a mean follow-up of 5.5 years, 151 persons developed AD. BMI averaged 27.4 at baseline and declined in about half the participants. In a proportional hazards model adjusted for age, sex, and education, each 1-unit less of BMI at baseline was associated with about a 5% increase in the risk of AD (hazard ratio = 0.944; 95% CI = 0.908 to 0.981), and each 1-unit annual decline in BMI (about the 10th percentile) was associated with about a 35% increase in the risk of AD compared with a person experiencing no change in BMI (about the 50th percentile) (hazard ratio = 0.730; 95% CI = 0.625 to 0.852). The results were similar after controlling for chronic diseases and excluding persons who developed AD during the first 4 years of observation. Random effects models showed that the rate of cognitive decline increased by about 8% for each 1-unit less of BMI at baseline and declined an additional 40%/year in persons losing 1 unit of BMI/year compared with those with no change in BMI.
Declining body mass index (BMI) is associated with increased risk of incident Alzheimer disease (AD). Loss of BMI may reflect pathologic processes that contribute to the subsequent development of AD.
How extinct, non-avian theropod dinosaurs locomoted is a subject of considerable interest, as is the manner in which it evolved on the line leading to birds. Fossil footprints provide the most direct ...evidence for answering these questions. In this study, step width—the mediolateral (transverse) distance between successive footfalls—was investigated with respect to speed (stride length) in non-avian theropod trackways of Late Triassic age. Comparable kinematic data were also collected for humans and 11 species of ground-dwelling birds. Permutation tests of the slope on a plot of step width against stride length showed that step width decreased continuously with increasing speed in the extinct theropods (p < 0.001), as well as the five tallest bird species studied (p < 0.01). Humans, by contrast, showed an abrupt decrease in step width at the walk–run transition. In the modern bipeds, these patterns reflect the use of either a discontinuous locomotor repertoire, characterized by distinct gaits (humans), or a continuous locomotor repertoire, where walking smoothly transitions into running (birds). The non-avian theropods are consequently inferred to have had a continuous locomotor repertoire, possibly including grounded running. Thus, features that characterize avian terrestrial locomotion had begun to evolve early in theropod history.
Background
Prehabilitation has emerged as a strategy to prepare patients for elective abdominal cancer surgery with documented improvements in postoperative outcomes. The aim of this study was to ...assess the evidence for prehabilitation interventions of relevance to the older adult.
Methods
Systematic searches were conducted using MEDLINE, Web of Science, Scopus, CINAHL and PsychINFO. Studies of preoperative intervention (prehabilitation) in patients undergoing abdominal cancer surgery reporting postoperative outcomes were included. Age limits were not set as preliminary searches revealed this would be too restrictive. Articles were screened and selected based on PRISMA guidelines, and assessment of bias was performed. Qualitative, quantitative and meta‐analyses of data were conducted as appropriate.
Results
Thirty‐three studies (3962 patients) were included. Interventions included exercise, nutrition, psychological input, comprehensive geriatric assessment and optimization, smoking cessation and multimodal (two or more interventions). Nine studies purposely selected high‐risk, frail or older patients. Thirty studies were at moderate or high risk of bias. Ten studies individually reported benefits in complication rates, with meta‐analyses for overall complications demonstrating significant benefit: multimodal (risk difference −0·1 (95 per cent c.i. −0·18 to −0·02); P = 0·01, I2 = 18 per cent) and nutrition (risk difference −0·18 (−0·26 to −0·10); P < 0·001, I2 = 0 per cent). Seven studies reported reductions in length of hospital stay, with no differences on meta‐analysis.
Conclusion
The conclusions of this review are limited by the quality of the included studies, and the heterogeneity of interventions and outcome measures reported. Exercise, nutritional and multimodal prehabilitation may reduce morbidity after abdominal surgery, but data specific to older patients are sparse.
Antecedentes
La pre‐habilitación ha surgido como una estrategia para preparar a los pacientes para la cirugía electiva del cáncer abdominal con mejoras documentadas en los resultados postoperatorios. El objetivo de este estudio fue evaluar la evidencia sobre las intervenciones de pre‐habilitación relevantes en adultos de edad avanzada.
Métodos
Se realizaron búsquedas sistemáticas utilizando MEDLINE, Web of Science, Scopus, CINAHL y PsychINFO. Registro PROSPERO: CRD42019120381. Se incluyeron estudios de intervención preoperatoria (pre‐habilitación) en pacientes sometidos a cirugía oncológica abdominal que describiesen resultados postoperatorios. No se fijaron límites en la edad dado que las búsquedas preliminares revelaron que ello sería demasiado restrictivo. Los artículos fueron examinados y seleccionados en base a las guías PRISMA y se realizó una evaluación del sesgo. Se llevó a cabo un análisis cualitativo, cuantitativo y metaanálisis de los datos según fuese apropiado.
Resultados
Se incluyeron 33 estudios (3.962 patients). Las intervenciones incluyeron ejercicio, nutrición, intervención psicológica, evaluación geriátrica global y optimización, abandono del tabaquismo y multimodal (dos o más intervenciones). Nueve estudios seleccionaron expresamente una población de pacientes de elevado riesgo, frágiles o de edad avanzada. Treinta estudios presentaban un riesgo moderado/alto de sesgo. Diez estudios describieron de forma individual beneficios en las tasas de complicaciones con metaanálisis para las complicaciones globales demostrando un beneficio significativo: multimodal (diferencia de riesgo ‐0,1 (i.c. del 95% −0,18 a −0,02); P = 0,01, I2 = 18%) e intervención nutricional (diferencia de riesgo −0,18 (i.c. del 95% −0,26 a −0,10); P < 0,001, I2 = 0%). Siete estudios describieron reducciones en la duración de la estancia hospitalaria, sin diferencias en el metaanálisis.
Conclusión
Las conclusiones de esta revisión están limitadas por la calidad de los estudios incluidos, heterogeneidad de las intervenciones y descripción de las medidas de resultados. Las intervenciones de pre‐habilitación de ejercicio, nutricionales y multimodales puede reducir la morbilidad tras cirugía abdominal, pero los datos concretos en pacientes de edad avanzada son escasos.
This systematic review and meta‐analysis suggests that multimodal and nutrition‐alone prehabilitation interventions may reduce postoperative complications and length of hospital stay. More high‐quality research is needed specifically on prehabilitation for older patients.
Use multimodal prehabilitation to reduce morbidity
We present a fast and efficient hybrid algorithm for selecting exoplanetary candidates from wide-field transit surveys. Our method is based on the widely used SysRem and Box Least-Squares (BLS) ...algorithms. Patterns of systematic error that are common to all stars on the frame are mapped and eliminated using the SysRem algorithm. The remaining systematic errors caused by spatially localized flat-fielding and other errors are quantified using a boxcar-smoothing method. We show that the dimensions of the search-parameter space can be reduced greatly by carrying out an initial BLS search on a coarse grid of reduced dimensions, followed by Newton–Raphson refinement of the transit parameters in the vicinity of the most significant solutions. We illustrate the method's operation by applying it to data from one field of the SuperWASP survey, comprising 2300 observations of 7840 stars brighter than V= 13.0. We identify 11 likely transit candidates. We reject stars that exhibit significant ellipsoidal variations caused indicative of a stellar-mass companion. We use colours and proper motions from the Two Micron All Sky Survey and USNO-B1.0 surveys to estimate the stellar parameters and the companion radius. We find that two stars showing unambiguous transit signals pass all these tests, and so qualify for detailed high-resolution spectroscopic follow-up.
Summary
Background
The mechanisms of sublingual immunotherapy (SLIT) are less well understood than those of subcutaneous immunotherapy (SCIT).
Objectives
To determine the effects of grass‐pollen SLIT ...on oral mucosal immune cells, local regulatory cytokines, serum allergen‐specific antibody subclasses and B cell IgE‐facilitated allergen binding (IgE‐FAB).
Methods
Biopsies from the sublingual mucosa of up to 14 SLIT‐treated atopics, nine placebo‐treated atopics and eight normal controls were examined for myeloid dendritic cells (mDCs) (CD1c), plasmacytoid dendritic cells (CD303), mast cells (AA1), T cells (CD3) and Foxp3 using immunofluorescence microscopy. IL‐10 and TGF‐β mRNA expression were identified by in situ hybridization. Allergen‐specific IgG and IgA subclasses and serum inhibitory activity for binding of allergen‐IgE complexes to B cells (IgE‐FAB) were measured before, during and on the completion of SLIT.
Results
Foxp3+ cells were increased in the oral epithelium of SLIT‐ vs. placebo‐treated atopics (P=0.04). Greater numbers of subepithelial mDCs were present in placebo‐treated, but not in SLIT‐treated, atopics compared with normal controls (P=0.05). There were fewer subepithelial mast cells and greater epithelial T cells in SLIT‐ compared with placebo‐treated atopics (P=0.1 for both). IgG1 and IgG4 were increased following SLIT (P<0.001). Peak seasonal IgA1 and IgA2 were increased during SLIT (P<0.05). There was a time‐dependent increase in serum inhibitory activity for IgE‐FAB in SLIT‐treated atopics.
Conclusions
SLIT with grass pollen extract is associated with increased Foxp3+ cells in the sublingual epithelium and systemic humoral changes as observed previously for SCIT.
Cite this as: G. W. Scadding, M. H. Shamji, M. R. Jacobson, D. I. Lee, D. Wilson, M. T. Lima, L. Pitkin, C. Pilette, K. Nouri‐Aria and S. R. Durham, Clinical & Experimental Allergy, 2010 (40) 598–606.
Unsustainable fishing simplifies food chains and, as with aquaculture, can result in reliance on a few economically valuable species. This lack of diversity may increase risks of ecological and ...economic disruptions. Centuries of intense fishing have extirpated most apex predators in the Gulf of Maine (United States and Canada), effectively creating an American lobster (Homarus americanusj monoculture. Over the past 20 years, the economic diversity of marine resources harvested in Maine has declined by almost 70%. Today, over 80% of the value of Maine's fish and seafood landings is from highly abundant lobsters. Inflationcorrected income from lobsters in Maine has steadily increased by nearly 400% since 1985. Fisheries managers, policy makers, and fishers view this as a success. However, such lucrative monocultures increase the social and ecological consequences of future declines in lobsters. In southern New England, disease and stresses related to increases in ocean temperature resulted in more than a 70% decline in lobster abundance, prompting managers to propose closing that fishery. A similar collapse in Maine could fundamentally disrupt the social and economic foundation of its coast. We suggest the current success of Maine's lobster fishery is a gilded trap. Gilded traps are a type of social trap in which collective actions resulting from economically attractive opportunities outweigh concerns over associated social and ecological risks or consequences. Large financial gain creates a strong reinforcing feedback that deepens the trap. Avoiding or escaping gilded traps requires managing for increased biological and economic diversity. This is difficult to do prior to a crisis while financial incentives for maintaining the status quo are large. The long-term challenge is to shift fisheries management away from single species toward integrated social-ecological approaches that diversify local ecosystems, societies, and economies. La pesca no sustentable simplifica las cadenas alimenticias y, como la acuicultura, puede resultar en una dependencia en unas cuantas especies valiosas económicamente. Esta falta de biodiversidad puede incrementar los riesgos de disrupciones ecológicas y económicas. Siglos de pesca intensiva ban extirpado a la mayoría de los depredadores superiores en el Golfo de Maine (E.U.A. y Canadá), creando efectivamente un monocultivo de langosta americana Homarus americanus). Durante los últimos 20 años, la diversidad económica de los recursos marinos cosechados en Maine ha declinado en casi 70%. Ahora, más de 80% del valor de las capturas de peces y mariscos consiste en langostas que son muy abundantes. El ingreso, corregido para la inflación, por langostas ha incrementado consistentemente en casi 400% desde 1985. Manejadores de pesquerías, políticos y Pescadores ven esto como un éxito. Sin embargo, tales monocultivos lucrativos incrementan las consecuencias sociales y ecológicas de declinaciones de langostas en el futuro. En el sur de Nueva Inglaterra, las enfermedades y los estreses relacionados con incrementos en la temperatura del océano resultaron en una declinación de mas de 70% en la abundancia de langostas, lo que obligó a la propuesta del cierre de esa pesquería. Un colapso similar en Maine podría desestabilizar la base social y económica de su costa. Sugerimos que el éxito actual de la pesquería de langosta en Maine es una trampa dorada. Las trampas doradas son un tipo de trampa social en el que las acciones colectivas derivadas de oportunidades atractivas económicamente sobrepasan a las preocupaciones por los riesgos o consecuencias ecológicas y sociales asociadas. El gran ingreso financiero crea una fuerte retroalimentación reforzante que profundiza la trampa. Escapar de o evitar las trampas doradas requiere de manejo para el incremento de la diversidad biológica y ecológica. Esto es difícil de hacer antes de una crisis mientras los incentivos financieros para mantener el status quo son grandes. El reto a largo plazo es cambiar el manejo de pesquerías de una sola especie hacia enfoques sociales-ecológicos integrados que diversifiquen los ecosistemas, las sociedades y las economías locales.
We describe the design and performance of the near-infrared (1.51-1.70 m), fiber-fed, multi-object (300 fibers), high resolution (R = λ/Δλ ∼ 22,500) spectrograph built for the Apache Point ...Observatory Galactic Evolution Experiment (APOGEE). APOGEE is a survey of ∼105 red giant stars that systematically sampled all Milky Way populations (bulge, disk, and halo) to study the Galaxy's chemical and kinematical history. It was part of the Sloan Digital Sky Survey III (SDSS-III) from 2011 to 2014 using the 2.5 m Sloan Foundation Telescope at Apache Point Observatory, New Mexico. The APOGEE-2 survey is now using the spectrograph as part of SDSS-IV, as well as a second spectrograph, a close copy of the first, operating at the 2.5 m du Pont Telescope at Las Campanas Observatory in Chile. Although several fiber-fed, multi-object, high resolution spectrographs have been built for visual wavelength spectroscopy, the APOGEE spectrograph is one of the first such instruments built for observations in the near-infrared. The instrument's successful development was enabled by several key innovations, including a "gang connector" to allow simultaneous connections of 300 fibers; hermetically sealed feedthroughs to allow fibers to pass through the cryostat wall continuously; the first cryogenically deployed mosaic volume phase holographic grating; and a large refractive camera that includes mono-crystalline silicon and fused silica elements with diameters as large as ∼400 mm. This paper contains a comprehensive description of all aspects of the instrument including the fiber system, optics and opto-mechanics, detector arrays, mechanics and cryogenics, instrument control, calibration system, optical performance and stability, lessons learned, and design changes for the second instrument.
Estimates of the rate of production of excited oxygen atoms due to the photolysis of ozone (J(O1D)) have been derived from radiation measurements carried out at Cape Grim, Tasmania (40.6 degree S, ...144.7 degree E). The individual measurements have a total uncertainty of 16 % (1 sigma ). These estimates agree well with model estimates of clear-sky photolysis rates. Observations spanning 2000-2005 have been used to quantify the impact of season, clouds and ozone column amount. The annual cycle of J(O1D) has been investigated via monthly means. These means show an interannual variation (monthly standard deviation) of 9 %, but in midsummer and midwinter this reduces to 3-5 %. Variations in solar zenith angle and total column ozone explain 86 % of the observed variability in the measured photolysis rates. The impact of total column ozone, expressed as a radiation amplification factor (RAF), is found to be ~ 1.53, in agreement with model estimates. This ozone dependence explains 20 % of the variation observed at medium solar zenith angles (30-50 degree ). The impact of clouds results in a median reduction of 30 % in J(O1D) for the same solar zenith angle range. Including estimates of cloudiness derived from long-wave radiation measurements resulted in a statistically significant fit to observations, but the quality of the fit did not increase significantly as measured by the adjusted R2.
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