Although screening mammography has delivered many benefits since its introduction in Canada in 1988, questions about perceived harms warrant an up-to-date review. To help oncologists and physicians ...provide optimal patient recommendations, the literature was reviewed to find the latest guidelines for screening mammography, including benefits and perceived harms of overdiagnosis, false positives, false negatives, and technologic advances. For women 40-74 years of age who actually participate in screening every 1-2 years, breast cancer mortality is reduced by 40%. With appropriate corrections, overdiagnosis accounts for 10% or fewer breast cancers. False positives occur in about 10% of screened women, 80% of which are resolved with additional imaging, and 10%, with breast biopsy. An important limitation of screening is the false negatives (15%-20%). The technologic advances of digital breast tomosynthesis, breast ultrasonography, and magnetic resonance imaging counter the false negatives of screening mammography, particularly in women with dense breast tissue.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK, VSZLJ
Aims
Soil respiration (R
s
) is a major pathway for carbon release to the atmosphere. We explored variability in dryland R
s
response to rainfall pulses at multiple levels of spatial heterogeneity: ...1) along a hyper-arid to arid rainfall gradient, 2) across soil surfaces that differ in stability and composition, and 3) among different geomorphic and vegetation patch types.
Methods
We measured in situ R
s
responses for 48 h following simulated rainfall pulses in the Namib Desert. Working across the rainfall gradient, we compared R
s
responses on two soil surfaces. Each soil surface had two vegetation/geomorphic patch types that differed in organic matter sources and transport processes, with one characterized by depositional inputs and one characterized by erosional losses.
Results
Soil respiration was highly responsive to rainfall pulses, although soil surfaces and patch types often exerted more control on R
s
than did rainfall pulses. Rainfall generally had proportionally greater influence on R
s
with higher annual rainfall. Greater R
s
occurred on stable than unstable soil surfaces and in depositional than erosional patch types.
Conclusions
Large differences in R
s
among rainfall zones, soil surfaces, and patch types point to the need to carefully consider multiple scales of spatial heterogeneity when interpreting dryland biogeochemical fluxes.
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BFBNIB, DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NMLJ, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In all living cells, the ribosome translates the genetic information carried by messenger RNAs (mRNAs) into proteins. The process of ribosome recycling, a key step during protein synthesis that ...ensures ribosomal subunits remain available for new rounds of translation, has been largely overlooked. Despite being essential to the survival of the cell, several mechanistic aspects of ribosome recycling remain unclear. In eubacteria and mitochondria, recycling of the ribosome into subunits requires the concerted action of the ribosome recycling factor (RRF) and elongation factor G (EF-G). Recently, the conserved protein HflX was identified in bacteria as an alternative factor that recycles the ribosome under stress growth conditions. The homologue of HflX, the GTP-binding protein 6 (GTPBP6), has a dual role in mitochondrial translation by facilitating ribosome recycling and biogenesis. In this review, mechanisms of ribosome recycling in eubacteria and mitochondria are described based on structural studies of ribosome complexes.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
Aminoglycosides are a class of antibiotics that bind to ribosomal RNA and exert pleiotropic effects on ribosome function. Amikacin, the semisynthetic derivative of kanamycin, is commonly used for ...treating severe infections with multidrug-resistant, aerobic Gram-negative bacteria. Amikacin carries the 4-amino-2-hydroxy butyrate (AHB) moiety at the N
amino group of the central 2-deoxystreptamine (2-DOS) ring, which may confer amikacin a unique ribosome inhibition profile. Here we use in vitro fast kinetics combined with X-ray crystallography and cryo-EM to dissect the mechanisms of ribosome inhibition by amikacin and the parent compound, kanamycin. Amikacin interferes with tRNA translocation, release factor-mediated peptidyl-tRNA hydrolysis, and ribosome recycling, traits attributed to the additional interactions amikacin makes with the decoding center. The binding site in the large ribosomal subunit proximal to the 3'-end of tRNA in the peptidyl (P) site lays the groundwork for rational design of amikacin derivatives with improved antibacterial properties.
Current lung cancer screening guidelines use mean diameter, volume or density of the largest lung nodule in the prior computed tomography (CT) or appearance of new nodule to determine the timing of ...the next CT. We aimed at developing a more accurate screening protocol by estimating the 3-year lung cancer risk after two screening CTs using deep machine learning (ML) of radiologist CT reading and other universally available clinical information.
A deep machine learning (ML) algorithm was developed from 25,097 participants who had received at least two CT screenings up to two years apart in the National Lung Screening Trial. Double-blinded validation was performed using 2,294 participants from the Pan-Canadian Early Detection of Lung Cancer Study (PanCan). Performance of ML score to inform lung cancer incidence was compared with Lung-RADS and volume doubling time using time-dependent ROC analysis. Exploratory analysis was performed to identify individuals with aggressive cancers and higher mortality rates.
In the PanCan validation cohort, ML showed excellent discrimination with a 1-, 2- and 3-year time-dependent AUC values for cancer diagnosis of 0·968±0·013, 0·946±0·013 and 0·899±0·017. Although high ML score cohort included only 10% of the PanCan sample, it identified 94%, 85%, and 71% of incident and interval lung cancers diagnosed within 1, 2, and 3 years, respectively, after the second screening CT. Furthermore, individuals with high ML score had significantly higher mortality rates (HR=16·07, p<0·001) compared to those with lower risk.
ML tool that recognizes patterns in both temporal and spatial changes as well as synergy among changes in nodule and non-nodule features may be used to accurately guide clinical management after the next scheduled repeat screening CT.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Purpose
To assess the cancer detection rate (CDR) in patients presenting with isolated breast pain.
Methods
A retrospective review was performed of consecutive patients presenting to a large tertiary ...care academic center or an affiliated hospital with isolated breast pain from October 1, 2013 to September 30, 2015. Medical records were reviewed for patient demographics, pain characteristics, imaging findings, and outcome.
Results
The study cohort was comprised of 971 exams in 953 patients, with a median age of 50 years. A total of 62.5% (607/971) of the cases were assessed by mammography and ultrasound, 24.4% (237/971) by ultrasound only, and 13.1% (127/971) by mammography only. Including the abnormalities detected in the asymptomatic breast, 88.7% (861/971) of the cases were negative or had benign findings (BI-RADS 1 and 2), 6.8% (66/971) were probably benign (BI-RADS 3), 3.9% (38/971) were suspicious (BI-RADS 4), and 0.6% (6/971) were highly suggestive of malignancy (BI-RADS 5). CDR on initial work-up was 0.8% (8/953), of which 0.6% (4/690) was in average-risk patients while 1.5% (4/263) was in higher-than-average risk patients.
Conclusions
CDR in patients presenting with isolated breast pain overall was low, comparable to the expected incidence of breast cancer in asymptomatic women. Work-up for isolated breast pain may therefore be unnecessary and lead to overutilization of healthcare resources. Routine screening mammography should be encouraged and higher-than-average risk patients may benefit from additional tests.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Background
Abbreviated breast MRI (A-MRI) substantially reduces the image acquisition and reading times and has been reported to have similar diagnostic accuracy as a full diagnostic ...protocol but has not been evaluated prospectively with respect to impact on psychological distress in women with a prior history of breast cancer (PHBC). This study aimed to determine if surveillance mammography (MG) plus A-MRI reduced psychological distress and if A-MRI improved cancer detection rates (CDR) as compared to MG alone.
Methods
This prospective controlled trial of parallel design was performed at a tertiary cancer center on asymptomatic women with PHBC who were randomized into two groups: routine surveillance with MG or intervention of MG plus A-MRI in a 1:1 ratio. Primary outcome was anxiety measured by four validated questionnaires at three different time-points during the study. Other parameters including CDR and positive predictive value for biopsy (PPV3) were compared between imaging modalities of MG and A-MRI. Tissue diagnoses or 1 year of follow-up were used to establish the reference standard. Linear mixed models were used to analyze anxiety measures and Fisher’s exact test to compare imaging outcomes.
Results
One hundred ninety-eight patients were allocated to either MG alone (94) or MG plus A-MRI (104). No significant group difference emerged for improvement in trait anxiety, worry and perceived health status (all Time-by-surveillance group interaction ps > .05). There was some advantage of A-MRI in reducing state anxiety at Time 2 (
p
< .05). Anxiety scores in all questionnaires were similarly elevated in both groups (50.99 ± 4.6 with MG alone vs 51.73 ± 2.56 with MG plus A-MRI,
p
> 0.05) and did not change over time. A-MRI detected 5 invasive cancers and 1 ductal carcinoma in situ (DCIS), and MG detected 1 DCIS. A-MRI had higher incremental CDR (48/1000(5/104) vs MG 5/1000(1/198,
p
= 0.01)) and higher biopsy rates (19.2% (20/104) vs MG 2.1% (2/94),
p
< 0.00001) with no difference in PPV3 (A-MRI 28.6% (6/21) vs MG 16.7% (1/6,
p
> .05).
Conclusion
There was no significant impact of A-MRI to patient anxiety or perceived health status. Compared to MG alone, A-MRI had significantly higher incremental cancer detection in PHBC. Despite a higher rate of biopsies, A-MRI had no demonstrable impact on anxiety, worry, and perceived health status.
Trial registration
ClinicalTrials.gov (
NCT02244593
). Prospectively registered on Sept. 14, 2014.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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