Objective To review the clinical outcomes of “ideal” vs “nonideal” postprostatectomy stress urinary incontinence (PPI) patients who underwent male sling placement. Methods The medical records of 95 ...consecutive patients with PPI who underwent male sling insertion (AdVance male sling, American Medical Systems, Minnetonka, MN) were reviewed. Patients were divided into “ideal” vs “nonideal” cohorts. The ideal group consisted of patients with mild to moderate incontinence (<4 pads/day or <300 g daily pad weight), ability to volitionally contract the external urinary sphincter, no history of pelvic radiation or cryotherapy, no history of previous anti-incontinence surgical procedures, the ability to generate a volitional detrusor contraction when voiding, and a postvoid residual urine volume <100 mL. Patients in the nonideal group did not satisfy all these criteria. Results Significant reductions in daily pad usage and weight were noted in both cohorts. In the ideal patient group, 66 of 72 patients (92%) would undergo the procedure again. Conversely, only 7 of 23 nonideal men (30%) would undergo the procedure again. Conclusion Preoperative patient selection can influence favorable outcomes after the treatment of PPI with AdVance male slings. Attention to ideal vs nonideal patient characteristics should be used when counseling men considering male sling surgery.
The K2K experiment observes indications of neutrino oscillation: a reduction of nu(mu) flux together with a distortion of the energy spectrum. Fifty-six beam neutrino events are observed in ...Super-Kamiokande (SK), 250 km from the neutrino production point, with an expectation of 80.1(+6.2)(-5.4). Twenty-nine one ring mu-like events are used to reconstruct the neutrino energy spectrum, which is better matched to the expected spectrum with neutrino oscillation than without. The probability that the observed flux at SK is explained by statistical fluctuation without neutrino oscillation is less than 1%.
METEOROLOGY, AIR QUALITY, AND HEALTH IN LONDON Bohnenstengel, S. I.; Belcher, S. E.; Aiken, A. ...
Bulletin of the American Meteorological Society,
05/2015, Letnik:
96, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Air quality and heat are strong health drivers, and their accurate assessment and forecast are important in densely populated urban areas. However, the sources and processes leading to high ...concentrations of main pollutants, such as ozone, nitrogen dioxide, and fine and coarse particulate matter, in complex urban areas are not fully understood, limiting our ability to forecast air quality accurately. This paper introduces the Clean Air for London (ClearfLo; www.clearflo.ac.uk) project’s interdisciplinary approach to investigate the processes leading to poor air quality and elevated temperatures.
Within ClearfLo, a large multi-institutional project funded by the U.K. Natural Environment Research Council (NERC), integrated measurements of meteorology and gaseous, and particulate composition/loading within the atmosphere of London, United Kingdom, were undertaken to understand the processes underlying poor air quality. Long-term measurement infrastructure installed at multiple levels (street and elevated), and at urban background, curbside, and rural locations were complemented with high-resolution numerical atmospheric simulations. Combining these (measurement–modeling) enhances understanding of seasonal variations in meteorology and composition together with the controlling processes. Two intensive observation periods (winter 2012 and the Summer Olympics of 2012) focus upon the vertical structure and evolution of the urban boundary layer; chemical controls on nitrogen dioxide and ozone production—in particular, the role of volatile organic compounds; and processes controlling the evolution, size, distribution, and composition of particulate matter. The paper shows that mixing heights are deeper over London than in the rural surroundings and that the seasonality of the urban boundary layer evolution controls when concentrations peak. The composition also reflects the seasonality of sources such as domestic burning and biogenic emissions.
Self-assembled particles of genetically engineered human L subunit ferritin expressing a silver-binding peptide were used as nanocontainers for the synthesis of silver nanoparticles. The inner cavity ...of the self-assembled protein cage displays a dodecapeptide that is capable of reducing silver ions to metallic silver. This chimeric protein cage when incubated in the presence of silver nitrate exhibits the growth of a silver nanocrystal within its cavity. Our studies indicate that it is possible to design chimeric cages, using specific peptide templates, for the growth of other inorganic nanoparticles.
The rapid proliferation of myeloid leukemia cells is highly dependent on increased glucose metabolism. Through an unbiased metabolomics analysis of leukemia cells, we found that the glycogenic ...precursor UDP-D-glucose is pervasively upregulated, despite low glycogen levels. Targeting the rate-limiting glycogen synthase 1 (GYS1) not only decreased glycolytic flux but also increased activation of the glycogen-responsive AMP kinase (AMPK), leading to significant growth suppression. Further, genetic and pharmacological hyper-activation of AMPK was sufficient to induce the changes observed with GYS1 targeting. Cancer genomics data also indicate that elevated levels of the glycogenic enzymes GYS1/2 or GBE1 (glycogen branching enzyme 1) are associated with poor survival in AML. These results suggest a novel mechanism whereby leukemic cells sustain aberrant proliferation by suppressing excess AMPK activity through elevated glycogenic flux and provide a therapeutic entry point for targeting leukemia cell metabolism.
Emerging data demonstrate important roles for the TYRO3/AXL/MERTK receptor tyrosine kinase (TAM RTK) family in diverse cancers. We investigated the prognostic relevance of GAS6 expression, encoding ...the common TAM RTK ligand, in 270 adults (n=71 aged<60 years; n=199 aged ⩾60 years) with de novo cytogenetically normal acute myeloid leukemia (CN-AML). Patients expressing GAS6 (GAS6+), especially those aged ⩾60 years, more often failed to achieve a complete remission (CR). In all patients, GAS6+ patients had shorter disease-free (DFS) and overall (OS) survival than patients without GAS6 expression (GAS6-). After adjusting for other prognostic markers, GAS6+ predicted CR failure (P=0.02), shorter DFS (P=0.004) and OS (P=0.04). To gain further biological insights, we derived a GAS6-associated gene-expression signature (P<0.001) that in GAS6+ patients included overexpressed BAALC and MN1, known to confer adverse prognosis in CN-AML, and overexpressed CXCL12, encoding stromal cell-derived factor, and its receptor genes, chemokine (C-X-C motif) receptor 4 (CXCR4) and CXCR7. This study reports for the first time that GAS6 expression is an adverse prognostic marker in CN-AML. Although GAS6 decoy receptors are not yet available in the clinic for GAS6+ CN-AML therapy, potential alternative therapies targeting GAS6+-associated pathways, for example, CXCR4 antagonists, may be considered for GAS6+ patients to sensitize them to chemotherapy.
Poly adenosine diphosphate (ADP)-ribose polymerase (PARP) is essential in cellular processing of DNA damage via the base excision repair pathway (BER). The PARP inhibition can be directly cytotoxic ...to tumour cells and augments the anti-tumour effects of DNA-damaging agents. This study evaluated the optimally tolerated dose of olaparib (4-(3--4-fluorophenyl) methyl-1(2H)-one; AZD2281, KU0059436), a potent PARP inhibitor, with dacarbazine and assessed safety, toxicity, clinical pharmacokinetics and efficacy of combination treatment.
Patients with advanced cancer received olaparib (20-200 mg PO) on days 1-7 with dacarbazine (600-800 mg m(-2) IV) on day 1 (cycle 2, day 2) of a 21-day cycle. An expansion cohort of chemonaive melanoma patients was treated at an optimally tolerated dose. The BER enzyme, methylpurine-DNA glycosylase and its substrate 7-methylguanine were quantified in peripheral blood mononuclear cells.
The optimal combination to proceed to phase II was defined as 100 mg bd olaparib with 600 mg m(-2) dacarbazine. Dose-limiting toxicities were neutropaenia and thrombocytopaenia. There were two partial responses, both in patients with melanoma.
This study defined a tolerable dose of olaparib in combination with dacarbazine, but there were no responses in chemonaive melanoma patients, demonstrating no clinical advantage over single-agent dacarbazine at these doses.
Early and late extremes in the timing of snowmelt have recently been observed in the Pacific Arctic. Subseasonal‐to‐seasonal forecasts of this timing are important for industry, environmental ...management, and Arctic communities. In northern Alaska, the timing is influenced by the advection of marine air from the north Pacific by the Aleutian Low, modulated by high pressure centered in the Beaufort Sea. A new climate index that integrates their interaction could advance melt predictions. We define this index based on 850‐hPa geopotential height at four fixed locations and refer to it as the Aleutian Low‐Beaufort Sea Anticyclone (ALBSA). During positive ALBSA in May, advection of +0.5‐1.5 K/day is observed through the Bering Strait. ALBSA is correlated with both snowmelt in northern Alaska and the onset of sea ice melt over the adjacent seas. ALBSA therefore may be suitable for monitoring the relevant circulation patterns and for developing predictive tools.
Plain Language Summary
Early and late extremes in the timing of snowmelt have recently been observed in northern Alaska. Forecasts of this timing with lead times of weeks to months are important for area stakeholders including industry, environmental managers, and Arctic communities. We find that transport of air masses from the north Pacific influences the timing of melt in the region. We introduce a new index called the Aleutian Low‐Beaufort Sea Anticyclone (ALBSA). When ALBSA is positive, warm Pacific air is observed over the Bering Strait and in the far western Arctic seas. ALBSA is correlated with the timing of spring melt and therefore may be suitable for both monitoring and prediction.
Key Points
Record early and late anomalies in the timing of snowmelt in northern Alaska have been observed from 2015‐2018
Timing of snowmelt is linked to atmospheric transport of air masses from the north Pacific
A climate index is introduced that is sensitive to the implicated advection and may be useful as a monitoring or prediction tool
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