ASXL1 mutations predict inferior molecular response to nilotinib treatment in chronic myeloid leukemia

Gene mutations independent of BCR::ABL1 have been identified in newly diagnosed patients with chronic myeloid leukemia (CML) in chronic phase, whereby mutations in epigenetic modifier genes were most common. These findings prompted the systematic analysis of prevalence, dynamics, and prognostic significance of such mutations, in a clinically well-characterized patient population of 222 CML patients from the TIGER study (CML-V) by targeted next-generation sequencing covering 54 myeloid leukemia-associated genes. In total, 53/222 CML patients (24%) carried 60 mutations at diagnosis with ASXL1 being most commonly affected (n = 20). To study mutation dynamics, longitudinal deep sequencing analysis of serial samples was performed in 100 patients after 12, 24, and 36 months of therapy. Typical patterns of clonal evolution included eradication, persistence, and emergence of mutated clones. Patients carrying an ASXL1 mutation at diagnosis showed a less favorable molecular response to nilotinib treatment, as a major molecular response (MMR) was achieved less frequently at month 12, 18, and 24 compared to all other patients. Patients with ASXL1 mutations were also younger and more frequently found in the high risk category, suggesting a central role of clonal evolution associated with ASXL1 mutations in CML pathogenesis

Drying and Rainfall Shape the Structure and Functioning of Nitrifying Microbial Communities in Riverbed Sediments

Non-flow periods in fluvial ecosystems are a global phenomenon. Streambed drying and rewetting by sporadic rainfalls could drive considerable changes in the microbial communities that govern stream nitrogen (N) availability at different temporal and spatial scales. We performed a microcosm-based experiment to investigate how dry period duration (DPD) (0, 3, 6, and 9 weeks) and magnitude of sporadic rewetting by rainfall (0, 4, and 21 mm applied at end of dry period) affected stocks of N in riverbed sediments, ammonia-oxidizing bacteria (AOB) and archaea (AOA) and rates of ammonia oxidation (AO), and emissions of nitrous oxide (N2O) to the atmosphere. While ammonium (NH4+) pool size decreased, nitrate (NO3−) pool size increased in sediments with progressive drying. Concomitantly, the relative and absolute abundance of AOB and, especially, AOA (assessed by 16S rRNA gene sequencing and quantitative PCR of ammonia monooxygenase genes) increased, despite an apparent decrease of AO rates with drying. An increase of N2O emissions occurred at early drying before substantially dropping until the end of the experiment. Strong rainfall of 21 mm increased AO rates and NH4+ in sediments, whereas modest rainfall of 4 mm triggered a notable increase of N2O fluxes. Interestingly, such responses were detected only after 6 and 9 weeks of drying. Our results demonstrate that progressive drying drives considerable changes in in-stream N cycling and the associated nitrifying microbial communities, and that sporadic rainfall can modulate these effects. Our findings are particularly relevant for N processing and transport in rivers with alternating dry and wet phases – a hydrological scenario expected to become more important in the future

Incidence of Surgical Site Infection Associated With Robotic Surgery

Objective. Robot-assisted surgery is minimally invasive and associated with less blood loss and shorter recovery time than open surgery. We aimed to determine the duration of robot-assisted surgical procedures and the incidence of postoperative surgical site infection (SSI) and to compare our data with the SSI incidence for open procedures according to national data. design. Retrospective cohort study. setting. A 689-bed academic medical center. patients. All patients who underwent a surgical procedure with use of a robotic surgical system during the period from 2000-2007. methods. SSIs were defined and procedure types were classified according to National Healthcare Safety Network criteria. National data for comparison were from 1992-2004. Because of small sample size, procedures were grouped according to surgical site or wound classification. results. Sixteen SSIs developed after 273 robot-assisted procedures (5.9%). The mean surgical duration was 333.6 minutes. Patients who developed SSI had longer mean surgical duration than did patients who did not (558 vs 318 minutes; ). The prostate P \u3c .001 and genitourinary group had 5.74 SSIs per 100 robot-assisted procedures (95% confidence interval [CI], 2.81-11.37), compared with 0.85 SSIs per 100 open procedures from national data. The gynecologic group had 10.00 SSIs per 100 procedures (95% CI, 2.79-30.10), compared with 1.72 SSIs per 100 open procedures. The colon and herniorrhaphy groups had 33.33 SSIs per 100 procedures (95% CI, 9.68-70.00) and 37.50 SSIs per 100 procedures (95% CI, 13.68-69.43), respectively, compared with 5.88 and 1.62 SSIs per 100 open procedures from national data. Patients with a clean-contaminated wound developed 6.1 SSIs per 100 procedures (95% CI, 3.5-10.3), compared with 2.59 SSIs per 100 open procedures. No significant differences in SSI rates were found for other groups. conclusions. Increased incidence of SSI after some types of robot-assisted surgery compared with traditional open surgery may be related to the learning curve associated with use of the robot

Stratified type inference for generalized algebraic data types

International audienceWe offer a solution to the type inference problem for an extension of Hindley and Milner's type system with generalized algebraic data types. Our approach is in two strata. The bottom stratum is a core language that marries type inference in the style of Hindley and Milner with type checking for generalized algebraic data types. This results in an extremely simple specification, where case constructs must carry an explicit type annotation and type conversions must be made explicit. The top stratum consists of (two variants of) an independent shape inference algorithm. This algorithm accepts a source term that contains some explicit type information, propagates this information in a local, predictable way, and produces a new source term that carries more explicit type information. It can be viewed as a preprocessor that helps produce some of the type annotations required by the bottom stratum. It is proven sound in the sense that it never inserts annotations that could contradict the type derivation that the programmer has in mind

Drying and Rainfall Shape the Structure and Functioning of Nitrifying Microbial Communities in Riverbed Sediments.

Non-flow periods in fluvial ecosystems are a global phenomenon. Streambed drying and rewetting by sporadic rainfalls could drive considerable changes in the microbial communities that govern stream nitrogen (N) availability at different temporal and spatial scales. We performed a microcosm-based experiment to investigate how dry period duration (DPD) (0, 3, 6, and 9 weeks) and magnitude of sporadic rewetting by rainfall (0, 4, and 21 mm applied at end of dry period) affected stocks of N in riverbed sediments, ammonia-oxidizing bacteria (AOB) and archaea (AOA) and rates of ammonia oxidation (AO), and emissions of nitrous oxide (N2O) to the atmosphere. While ammonium (NH4 +) pool size decreased, nitrate (NO3 -) pool size increased in sediments with progressive drying. Concomitantly, the relative and absolute abundance of AOB and, especially, AOA (assessed by 16S rRNA gene sequencing and quantitative PCR of ammonia monooxygenase genes) increased, despite an apparent decrease of AO rates with drying. An increase of N2O emissions occurred at early drying before substantially dropping until the end of the experiment. Strong rainfall of 21 mm increased AO rates and NH4 + in sediments, whereas modest rainfall of 4 mm triggered a notable increase of N2O fluxes. Interestingly, such responses were detected only after 6 and 9 weeks of drying. Our results demonstrate that progressive drying drives considerable changes in in-stream N cycling and the associated nitrifying microbial communities, and that sporadic rainfall can modulate these effects. Our findings are particularly relevant for N processing and transport in rivers with alternating dry and wet phases - a hydrological scenario expected to become more important in the future