Background
Early observational data suggest that this approach is safe and feasible, but it is technically challenging and the learning curve has not yet been determined. The objective of this study ...was to determine the number of cases required achieve proficiency in transanal total mesorectal excision (TA-TME) for rectal adenocarcinoma.
Methods
All TA-TME cases performed from 03/2012-01/2017 at a single high-volume tertiary care institution for rectal adenocarcinoma were included. A cumulative summation (CUSUM) analysis was performed to determine the number of cases required to reach proficiency, defined as high-quality TME (complete or near-complete mesorectal envelope, negative distal (DRM), and circumferential resection (> 1 mm; CRM) margin). The acceptable and unacceptable rates of good quality TME were defined based on the incidence of high-quality TME in laparoscopic (unacceptable rate = 81.7%) and open (acceptable rate = 86.9%) arms of the ACOSOG Z6051 trial.
Results
A total of 87 consecutive cases were included with mean tumor height 4.8 cm (SD 2.7) and 80% (70/87) received neoadjuvant chemoradiation. Post-operative morbidity occurred in 44% (38/87) of cases, including 21% (18/87) readmissions. Median length of stay was 4 days IQR 3–8. A good quality TME was performed in 95% (83/87) of cases including 98% (85/87) negative CRM, 99% (86/87) negative DRM, and 99% (86/87) complete or near-complete mesorectal envelope. CUSUM analysis reported that the good quality TME rate reaches an acceptable rate after 51 cases overall, and 45 cases if abdominoperineal resections are excluded.
Conclusion
TA-TME is a complex technique that requires a minimum of 45–51 cases to reach an acceptable incidence of high-quality TME and lower operative duration.
We present the results of a search for heavy QCD axions performed by the ArgoNeuT experiment at Fermilab. We search for heavy axions produced in the NuMI neutrino beam target and absorber decaying ...into dimuon pairs, which can be identified using the unique capabilities of ArgoNeuT and the MINOS near detector. This decay channel is motivated by a broad class of heavy QCD axion models that address the strong CP and axion quality problems with axion masses above the dimuon threshold. We obtain new constraints at a 95% confidence level for heavy axions in the previously unexplored mass range of 0.2-0.9 GeV, for axion decay constants around tens of TeV.
Glyburide's pharmacokinetics (PK) and pharmacodynamics have not been studied in women with gestational diabetes mellitus (GDM). The objective of this study was to assess steady‐state PK of glyburide, ...as well as insulin sensitivity, β‐cell responsivity, and overall disposition indices after a mixed‐meal tolerance test (MMTT) in women with GDM (n = 40), nonpregnant women with type 2 diabetes mellitus (T2DM) (n = 26), and healthy pregnant women (n = 40, MMTT only). At equivalent doses, glyburide plasma concentrations were ~50% lower in pregnant women than in nonpregnant subjects. The average umbilical cord/maternal plasma glyburide concentration ratio at the time of delivery was 0.7 ± 0.4. Insulin sensitivity was approximately fivefold lower in women with GDM as compared with healthy pregnant women. Despite comparable β‐cell responsivity indices, the average β‐cell function corrected for insulin resistance was more than 3.5‐fold lower in women with glyburide‐treated GDM than in healthy pregnant women. Women with GDM in whom glyburide treatment has failed may benefit from alternative medication or dosage escalation; however, fetal safety should be kept in mind.
Clinical Pharmacology & Therapeutics (2009); 85, 6, 607–614 doi:10.1038/clpt.2009.5
Focusing laser light onto a very small target can produce the conditions for laboratory-scale nuclear fusion of hydrogen isotopes. The lack of accurate predictive models, which are essential for the ...design of high-performance laser-fusion experiments, is a major obstacle to achieving thermonuclear ignition. Here we report a statistical approach that was used to design and quantitatively predict the results of implosions of solid deuterium-tritium targets carried out with the 30-kilojoule OMEGA laser system, leading to tripling of the fusion yield to its highest value so far for direct-drive laser fusion. When scaled to the laser energies of the National Ignition Facility (1.9 megajoules), these targets are predicted to produce a fusion energy output of about 500 kilojoules-several times larger than the fusion yields currently achieved at that facility. This approach could guide the exploration of the vast parameter space of thermonuclear ignition conditions and enhance our understanding of laser-fusion physics.
ULTRACAM is a portable, high-speed imaging photometer designed to study faint astronomical objects at high temporal resolutions. ULTRACAM employs two dichroic beamsplitters and three frame-transfer ...CCD cameras to provide three-colour optical imaging at frame rates of up to 500 Hz. The instrument has been mounted on both the 4.2-m William Herschel Telescope on La Palma and the 8.2-m Very Large Telescope in Chile, and has been used to study white dwarfs, brown dwarfs, pulsars, black hole/neutron star X-ray binaries, gamma-ray bursts, cataclysmic variables, eclipsing binary stars, extrasolar planets, flare stars, ultracompact binaries, active galactic nuclei, asteroseismology and occultations by Solar System objects (Titan, Pluto and Kuiper Belt objects). In this paper we describe the scientific motivation behind ULTRACAM, present an outline of its design and report on its measured performance.
Tumour location may affect oncologic outcomes for colon adenocarcinoma due to different levels of vascular ligation and nodal harvest, but the data are equivocal. The objective of this study is to ...determine the effect of tumor location and lymph node yield on overall survival(OS) in stage I-III colon adenocarcinoma.
The 2004–2014 National Cancer Database was queried for colectomies for non-metastatic colon adenocarcinoma, excluding transverse colon and rectal cancer. Patients were grouped based on left/right tumor location. Main outcome measure was 5-year OS. Propensity score matching created balanced cohorts. Multilevel survival analysis determined the independent effect of tumor location and nodal harvest on OS.
There were 504,958 patients (273,198 right; 231,760 left) in the entire cohort: 26.4% stage-I, 37.3% stage-II, and 36.3% stage-III (equal distribution left/right). After 1:1 matching(n = 297,080), right cancers were associated with worse 5-year overall survival for stage-II (66% vs. 70%, p < 0.001) and -III (56% vs. 60%, p < 0.001) despite similar nodal harvest and proportion receiving systemic therapy. On multivariate analysis, right-sided cancers (HR 1.12, 95%CI 1.06–1.19) had worse OS, independent of stage and nodal harvest. Nodal harvest ≥22 nodes had the highest OS (HR 0.71, 95%CI 0.68–0.75). There was an interaction between right-sided cancer and >22 lymph node harvest towards increased survival (HR 0.86, 95%CI 0.80–0.92).
Right-sided cancers are associated with worse oncologic outcomes compared to left-sided tumors but a higher lymph node yield improves survival. These data provide indirect evidence for a higher lymphatic harvest to improve survival.
•5-year overall survival for left- and right-sided colon cancer was compared.•Right cancers were associated with worse 5-year overall survival for stage-II and -III.•Increased nodal harvest (≥22 nodes) had the highest survival.•Higher nodal harvest improved survival for right-more than left-sided lesions.
Large, intact areas of tropical peatland are highly threatened at a global scale by the expansion of commercial agriculture and other forms of economic development. Conserving peatlands on a ...landscape scale, with their hydrology intact, is of international conservation importance to preserve their distinctive biodiversity and ecosystem services and maintain their resilience to future environmental change. We explored threats to and opportunities for conserving remaining intact tropical peatlands; thus, we excluded peatlands of Indonesia and Malaysia, where extensive deforestation, drainage, and conversion to plantations means conservation in this region can protect only small fragments of the original ecosystem. We focused on a case study, the Pastaza-Marañón Foreland Basin (PMFB) in Peru, which is among the largest known intact tropical peatland landscapes in the world and is representative of peatland vulnerability. Maintenance of the hydrological conditions critical for carbon storage and ecosystem function of peatlands is, in the PMFB, primarily threatened by expansion of commercial agriculture linked to new transport infrastructure that is facilitating access to remote areas. There remain opportunities in the PMFB and elsewhere to develop alternative, more sustainable land-use practices. Although some of the peatlands in the PMFB fall within existing legally protected areas, this protection does not include the most carbon-dense (domed pole forest) areas. New carbon-based conservation instruments (e.g., REDD+, Green Climate Fund), developing markets for sustainable peatland products, transferring land title to local communities, and expanding protected areas offer pathways to increased protection for intact tropical peatlands in Amazonia and elsewhere, such as those in New Guinea and Central Africa which remain, for the moment, broadly beyond the frontier of commercial development. Extensas e intactas áreas de turberas tropicales están severamente amenazadas a escala mundial, debido a la expansión de la agricultura comercial y a otras formas de desarrollo económico. La conservación de las turberas como parte del medio natural, con su hidrología no intervenida, es de importancia internacional para asegurar la conservación de su biodiversidad tan característica y de los servicios ambientales que ofrecen, y así mantener su resiliencia ante futuros cambios ambientales. Exploramos las amenazas y las oportunidades para conservar las turberas tropicales intactas y remanentes. Nuestro enfoque por lo tanto excluye las turberas de Indonesia y Malasia, donde la deforestación de forma extensiva y el drenado para el establecimiento de plantaciones hace que la conservación en estas regiones pueda proteger solo pequeños fragmentos del ecosistema original En este estudio, nos enfocamos en las cuencas del Pastaza Marañón (PMFB, siglas en inglés) en Perú, que comprende una de las turberas tropicales intactas más extensas del mundo y es representativa de la vulnerabilidad que las amenaza. El mantenimiento de las condiciones hidrológicas críticas para el almacenamiento de carbono y la función ambiental de las turberas está, en la PMFB, amenazada principalmente por la expansión de la agricultura comercial y las nuevas vías de transporte que facilitan el acceso a las áreas remotas. En la PMFB y en otros lugares aún hay oportunidades para desarrollar prácticas alternativas y sostenibles del uso del suelo. Aunque algunas de las turberas en la PMFB caen dentro de áreas naturales protegidas, esta protección no incluye las áreas con mayor densidad de carbono (varillal hidromórfico). Nuevas herramientas para la conservación basada en el carbono (p.e. REDD+, Fondo Verde para el Clima), el desarrollo de mercados para los productos de las turberas, la transferencia de títulos de propiedad de la tierra a las comunidades locales, y la expansión de las áreas protegidas ofrecen alternativas para una mayor protección de las turberas tropicales intactas en la Amazonia y en otros lugares, como las turberas de Nueva Guinea y África Central que permanecen, por el momento, alejadas de la frontera de desarrollo comercial.
•We reveal relationships between acute malaria infection and sparrow immune responses.•Glucocorticoid negative feedback strengthened after P. relictum infection.•Liver TNF-α expression was positively ...correlated with peak parasitemia.•Infected sparrows exhibited an anti-inflammatory profile during acute infection.•Infected sparrows’ baseline glucose and liver IFN-γ expression predicted immunity.
Hosts of the same species vary in physiological responses to the same parasite, and some groups of individuals can disproportionately affect disease dynamics; however, the underlying pathophysiology of host-parasite interactions is poorly understood in wildlife. We tested the hypothesis that the hypothalamic–pituitary–adrenal (HPA) axis mediates host resistance and tolerance to avian malaria during the acute phase of infection by evaluating whether individual variation in circulating glucocorticoids predicted resistance to avian malaria in a songbird. We experimentally inoculated wild-caught house sparrows (Passer domesticus) with naturally sourced Plasmodium relictum and quantified baseline and restraint-induced circulating corticosterone, negative feedback ability, cellular and humoral immune function, and baseline and restraint-induced glycemia, prior to and during acute malaria infection. During peak parasitemia, we also evaluated the expression of several liver cytokines that are established pathological hallmarks of malaria in mammals: two pro-inflammatory (IFN-γ and TNF-α) and two anti-inflammatory (IL-10 and TGF-β). Although most of the host metrics we evaluated were not correlated with host resistance or tolerance to avian malaria, this experiment revealed novel relationships between malarial parasites and the avian immune system that further our understanding of the pathology of malaria infection in birds. Specifically, we found that: (1) TNF-α liver expression was positively correlated with parasitemia; (2) sparrows exhibited an anti-inflammatory profile during malaria infection; and (3) IFN-γ and circulating glucose were associated with several immune parameters, but only in infected sparrows. We also found that, during the acute phase of infection, sparrows increased the strength of corticosterone negative feedback at the level of the pituitary. In the context of our results, we discuss future methodological considerations and aspects of host physiology that may confer resistance to avian malaria, which can help inform conservation and rehabilitation strategies for avifauna at risk.
Background Centralization of care to “centers of excellence” in Europe has led to improved oncologic outcomes; however, little is known regarding the impact of nonmandated regionalization of rectal ...cancer care in the United States. Methods The Statewide Planning and Research Cooperative System (SPARCS) was queried for elective abdominoperineal and low anterior resections for rectal cancer from 2000 to 2011 in New York with the use of International Classification of Diseases, Ninth Revision codes. Surgeon volume and hospital volume were grouped into quartiles, and high-volume surgeons (≥10 resections/year) and hospitals (≥25 resections/year) were defined as the top quartile of annual caseload of rectal cancer resection and compared with the bottom 3 quartiles during analyses. Bivariate and multilevel regression analyses were performed to assess factors associated with restorative procedures, 30-day mortality, and temporal trends in these endpoints. Results Among 7,798 rectal cancer resections, the overall rate of no-restorative proctectomy and 30-day mortality decreased by 7.7% and 1.2%, respectively, from 2000 to 2011. In addition, there was a linear increase in the proportion of cases performed by both high-volume surgeons and high-volume hospitals and a decrease in the number of surgeons and hospitals performing rectal cancer surgery. High-volume surgeons at high-volume hospitals were associated independently with both less nonrestorative proctectomies (odds ratio 0.65, 95% confidence interval 0.48–0.89) and mortality (odds ratio 0.43, 95% confidence interval 0.21–0.87) rates. No patterns of significant improvement within the volume strata of the surgeon and hospitals were observed over time. Conclusion This study suggests that the current trend toward regionalization of rectal cancer care to high-volume surgeons and high-volume centers has led to improved outcomes. These findings have implications regarding the policy of health care delivery in the United States, supporting referral to high-volume centers of excellence.
Novel object trials are commonly used to assess aversion to novelty (neophobia), and previous work has shown neophobia can be influenced by the social environment, but whether the altered behaviour ...persists afterwards (social learning) is largely unknown in wild animals. We assessed house sparrow (
) novel object responses before, during and after being paired with a conspecific of either similar or different behavioural phenotype. During paired trials, animals housed with a similar or more neophobic partner demonstrated an increased aversion to novel objects. This change did not persist a week after unpairing, but neophobia decreased after unpairing in birds previously housed with a less neophobic partner. We also compared novel object responses to non-object control trials to validate our experimental procedure. Our results provide evidence of social learning in a highly successful invasive species, and an interesting asymmetry in the effects of social environment on neophobia behaviour depending on the animal's initial behavioural phenotype.
PDF
