Five-year survival after surgical treatment for kidney cancer

BACKGROUND. Kidney cancer's rising incidence is largely attributable to the increased detection of small renal masses. Although surgery rates have paralleled this incidence trend, mortality continues to rise, calling into question the necessity of surgery for all patients with renal masses. Using a population-based cohort, a competing risk analysis was performed to estimate patient survival after surgery for kidney cancer, as a function of patient age and tumor size at diagnosis. METHODS. With data from the Surveillance, Epidemiology, and End Results Program (1983–2002), a cohort was assembled of 26,618 patients with surgically treated, local-regional kidney cancer. Patients were sorted into 20 age-tumor size categories and the numbers of patients that were alive, dead from kidney cancer, and dead from other causes were tabulated. Poisson regression models were fitted to obtain estimates of cancer-specific and competing-cause mortality. RESULTS. Age-specific kidney cancer mortality was stable across all size strata but varied inversely with tumor size. Patients with the smallest tumors enjoyed the lowest cancer-specific mortality (5% for masses ≤4 cm). Competing-cause mortality rose with increasing patient age. The estimated 5-year competing-cause mortality for elderly subjects (≥70 years) was 28.2% (95% confidence interval [CI]: 25.9%–30.8%), irrespective of tumor size. CONCLUSIONS. Despite surgical therapy, competing-cause mortality for patients with renal masses rises with increasing patient age. After 5 years, one-third of elderly patients (≥70 years) will die from other causes, suggesting the need for prospective studies to evaluate the role of active surveillance as an initial therapeutic approach for some small renal masses. Cancer 2007. © 2007 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55991/1/22600_ftp.pd

Essential and checkpoint functions of budding yeast ATM and ATR during meiotic prophase are facilitated by differential phosphorylation of a meiotic adaptor protein, Hop1

A hallmark of the conserved ATM/ATR signalling is its ability to mediate a wide range of functions utilizing only a limited number of adaptors and effector kinases. During meiosis, Tel1 and Mec1, the budding yeast ATM and ATR, respectively, rely on a meiotic adaptor protein Hop1, a 53BP1/Rad9 functional analog, and its associated kinase Mek1, a CHK2/Rad53-paralog, to mediate multiple functions: control of the formation and repair of programmed meiotic DNA double strand breaks, enforcement of inter-homolog bias, regulation of meiotic progression, and implementation of checkpoint responses. Here, we present evidence that the multi-functionality of the Tel1/Mec1-to-Hop1/Mek1 signalling depends on stepwise activation of Mek1 that is mediated by Tel1/Mec1 phosphorylation of two specific residues within Hop1: phosphorylation at the threonine 318 (T318) ensures the transient basal level Mek1 activation required for viable spore formation during unperturbed meiosis. Phosphorylation at the serine 298 (S298) promotes stable Hop1-Mek1 interaction on chromosomes following the initial phospho-T318 mediated Mek1 recruitment. In the absence of Dmc1, the phospho-S298 also promotes Mek1 hyper-activation necessary for implementing meiotic checkpoint arrest. Taking these observations together, we propose that the Hop1 phospho-T318 and phospho-S298 constitute key components of the Tel1/Mec1- based meiotic recombination surveillance (MRS) network and facilitate effective coupling of meiotic recombination and progression during both unperturbed and challenged meiosis

Multiexcitons confined within a sub-excitonic volume: Spectroscopic and dynamical signatures of neutral and charged biexcitons in ultrasmall semiconductor nanocrystals

The use of ultrafast gating techniques allows us to resolve both spectrally and temporally the emission from short-lived neutral and negatively charged biexcitons in ultrasmall (sub-10 nm) CdSe nanocrystals (nanocrystal quantum dots). Because of forced overlap of electronic wave functions and reduced dielectric screening, these states are characterized by giant interaction energies of tens (neutral biexcitons) to hundreds (charged biexcitons) of meV. Both types of biexcitons show extremely short lifetimes (from sub-100 picoseconds to sub-picosecond time scales) that rapidly shorten with decreasing nanocrystal size. These ultrafast relaxation dynamics are explained in terms of highly efficient nonradiative Auger recombination.Comment: 5 pages, 4 figures, to be published in Phys. Rev.

The 72-Hour WEBT Microvariability Observation of Blazar S5 0716+714 in 2009

Context. The international whole earth blazar telescope (WEBT) consortium planned and carried out three days of intensive micro-variability observations of S5 0716+714 from February 22, 2009 to February 25, 2009. This object was chosen due to its bright apparent magnitude range, its high declination, and its very large duty cycle for micro-variations. Aims. We report here on the long continuous optical micro-variability light curve of 0716+714 obtained during the multi-site observing campaign during which the Blazar showed almost constant variability over a 0.5 magnitude range. The resulting light curve is presented here for the first time. Observations from participating observatories were corrected for instrumental differences and combined to construct the overall smoothed light curve. Methods. Thirty-six observatories in sixteen countries participated in this continuous monitoring program and twenty of them submitted data for compilation into a continuous light curve. The light curve was analyzed using several techniques including Fourier transform, Wavelet and noise analysis techniques. Those results led us to model the light curve by attributing the variations to a series of synchrotron pulses. Results. We have interpreted the observed microvariations in this extended light curve in terms of a new model consisting of individual stochastic pulses due to cells in a turbulent jet which are energized by a passing shock and cool by means of synchrotron emission. We obtained an excellent fit to the 72-hour light curve with the synchrotron pulse model

Scotland’s biodiversity progress to 2020 Aichi Targets:Conserving genetic diversity- development of a national approach for addressing Aichi Biodiversity Target 13 that includes wild species

Aichi Target 13 (T13) focuses on the conservation of genetic diversity. •Major challenges in implementing T13 are that the type of genetic diversity to conserve is not clearly defined, and that key issues in genetic conservation vary across different sectors (e.g., forestry vs agriculture vs other species of socio-economic importance). •In Scotland and the UK more widely, baseline mechanisms are well established for assessing and reporting on genetic diversity in species of agricultural importance (e.g., rare livestock breeds, crop wild relatives), and a methodology has been established for ornamental plants. •A new UK Strategy for Forest Genetics Resources was launched in 2019, creating a framework for linking forest trees into T13 reporting. •However, there is no clear strategy to deal with ‘other species of socio-economic importance’ in Scotland, the UK or indeed elsewhere, and addressing this gap is the major focus of this report. •There is a lack of guidance for identifying focal species of socio-economic importance, and no clear mechanism for addressing T13 for these species once they have been identified. •To address this, we have identified a set of criteria for defining terrestrial and freshwater species of socio-economic importance in Scotland, and selected an initial list of 26 species. •The criteria applied were: -National conservation priority wild species. -Species of national cultural importance. -Species providing key ecosystem services. -Species of importance for wild harvesting (food and medicine). -Economically important game species. •We then developed a simple, readily applicable scorecard method for assessing risks to the conservation of genetic diversity in these species. •The scorecard approach is not dependent on prior genetic knowledge, and instead uses structured expert opinion assessments of whether: -Demographic declines are likely to lead to loss of genetic diversity (genetic erosion). -Hybridisation is likely to lead to undesirable replacement of genetic diversity. -Restrictions to regeneration/turnover are likely to impede evolutionary change. •For plant species where seed-banking is a viable mechanism for holding genetic resources ex situ,we also report on the representativeness of these ex situ collections. •Overall, this scorecard provides a mechanism for incorporating ‘other species of socio-economic importance’ into T13 actions and reporting. •Furthermore, its application is not restricted to Aichi T13 as the approach is designed as a generic scorecard for genetic diversity. It is thus relevant to post-2020 CBD targets focusing on genetic diversity. •Future priorities include: -Extension to other species of socio-economic, commercial and cultural importance (with the inclusion of marine species being a particularly high priority). -Harmonising genetic conservation strategies between sectors (drawing on commonalities), whilst minimising disruption of existing well-established methodologies within sectors. -Greater incorporation of genomic data into monitoring genetic diversity (particularly in the agricultural and forestry sectors where data availability is potentially high)

Retroperitoneoscopic radical nephrectomy with a small incision for renal cell carcinoma: Comparison with the conventional method

<p>Abstract</p> <p>purpose</p> <p>When retroperitoneoscopic radical nephrectomy for renal cell carcinoma was introduced into our institution, we performed a combined small skin incision method. In this method, a small incision was made to approach the retroperitoneal space prior to setting trockers and thereafter a LAPDISC was placed in the incision to start the retroperitoneoscopic procedure. In this study, we compared the outcomes between the combined small skin incision method ("A method" hereinafter) and the conventional method ("B method" hereinafter).</p> <p>material and methods</p> <p>Among the cases of T1N0M0 suspicious renal cell carcinoma treated at Yokohama City University between May 2003 and June 2009, the A method was performed in 51 cases and the B method was performed in 33 cases. The factors in the outcomes compared between the A and B methods were the duration of procedure, volume of bleeding, volume of transfusion, weight of the specimen, incidence of peritoneal injury, rate of conversion to open surgery, and perioperative complications.</p> <p>results</p> <p>The duration of the procedure was 214.4 ± 46.9 minutes in the A method group and 208.1 ± 36.4 minutes in the B method group (p = 0.518). The volume of bleeding and the weight of the specimen were 105.5 ± 283.2 ml and 335.1 ± 137.4 g in the A method group and 44.8 ± 116 ml (p = 0.247) and 309.2 ± 126 g (p = 0.385) in the B method group. There was no significant difference in all factors analyzed.</p> <p>conclusion</p> <p>The A method would be highly possible to produce stable results, even during the introduction period when the staff and the institution are still unfamiliar with the retroperitoneoscopic surgery.</p

SIRT1-NOX4 Signaling Axis Regulates Cancer Cachexia

Approximately one third of cancer patients die due to complexities related to cachexia. However, the mechanisms of cachexia and the potential therapeutic interventions remain poorly studied. We observed a significant positive correlation between SIRT1 expression and muscle fiber cross-sectional area in pancreatic cancer patients. Rescuing Sirt1 expression by exogenous expression or pharmacological agents reverted cancer cell-induced myotube wasting in culture conditions and mouse models. RNA-seq and follow-up analyses showed cancer cell-mediated SIRT1 loss induced NF-κB signaling in cachectic muscles that enhanced the expression of FOXO transcription factors and NADPH oxidase 4 (Nox4), a key regulator of reactive oxygen species production. Additionally, we observed a negative correlation between NOX4 expression and skeletal muscle fiber cross-sectional area in pancreatic cancer patients. Knocking out Nox4 in skeletal muscles or pharmacological blockade of Nox4 activity abrogated tumor-induced cachexia in mice. Thus, we conclude that targeting the Sirt1-Nox4 axis in muscles is an effective therapeutic intervention for mitigating pancreatic cancer-induced cachexia