Assessment of the 2020 NICE criteria for preoperative radiotherapy in patients with rectal cancer treated by surgery alone in comparison with proven MRI prognostic factors: a retrospective cohort study

BACKGROUND: Selection of patients for preoperative treatment in rectal cancer is controversial. The new 2020 National Institute for Health and Care Excellence (NICE) guidelines, consistent with the National Comprehensive Cancer Network guidelines, recommend preoperative radiotherapy for all patients except for those with radiologically staged T1-T2, N0 tumours. We aimed to assess outcomes in non-irradiated patients with rectal cancer and to stratify results on the basis of NICE criteria, compared with known MRI prognostic factors now omitted by NICE. METHODS: For this retrospective cohort study, we identified patients undergoing primary resectional surgery for rectal cancer, without preoperative radiotherapy, at Basingstoke Hospital (Basingstoke, UK) between Jan 1, 2011, and Dec 31, 2016, and at St Marks Hospital (London, UK) between Jan 1, 2007, and Dec 31, 2017. Patients with MRI-detected extramural venous invasion, MRI-detected tumour deposits, and MRI-detected circumferential resection margin involvement were categorised as MRI high-risk for recurrence (local or distant), and their outcomes (disease-free survival, overall survival, and recurrence) were compared with patients defined as high-risk according to NICE criteria (MRI-detected T3+ or MRI-detected N+ status). Kaplan-Meier and Cox proportional hazards analyses were used to compare the groups. FINDINGS: 378 patients were evaluated, with a median of 66 months (IQR 44-95) of follow up. 22 (6%) of 378 patients had local recurrence and 68 (18%) of 378 patients had distant recurrence. 248 (66%) of 378 were classified as high-risk according to NICE criteria, compared with 121 (32%) of 378 according to MRI criteria. On Kaplan-Meier analysis, NICE high-risk patients had poorer 5-year disease-free survival compared with NICE low-risk patients (76% [95% CI 70-81] vs 87% [80-92]; hazard ratio [HR] 1·91 [95% CI 1·20-3·03]; p=0·0051) but not 5-year overall survival (80% [74-84] vs 88% [81-92]; 1·55 [0·94-2·53]; p=0·077). MRI criteria separated patients into high-risk versus low-risk groups that predicted 5-year disease-free survival (66% [95% CI 57-74] vs 88% [83-91]; HR 3·01 [95% CI 2·02-4·47]; p<0·0001) and 5-year overall survival (71% [62-78] vs 89% [84-92]; 2·59 [1·62-3·88]; p<0·0001). On multivariable analysis, NICE risk assessment was not associated with either disease-free survival or overall survival, whereas MRI criteria predicted disease-free survival (HR 2·74 [95% CI 1·80-4·17]; p<0·0001) and overall survival (HR 2·44 [95% CI 1·51-3·95]; p=0·00027). 139 NICE high-risk patients who were defined as low-risk based on MRI criteria had similar disease-free survival as 118 NICE low-risk patients; therefore, 37% (139 of 378) of patients in this study cohort would have been overtreated with NICE 2020 guidelines. Of the 130 patients defined as low-risk by NICE guidelines, 12 were defined as high-risk on MRI risk stratification and would have potentially been missed for treatment. INTERPRETATION: Compared to previous guidelines, implementation of the 2020 NICE guidelines will result in significantly more patients receiving preoperative radiotherapy. High-quality MRI selects patients with good outcomes (particularly low local recurrence) without radiotherapy, with little margin for improvement. Overuse of radiotherapy could occur with this unselective approach. The high-risk group, with the most chance of benefiting from preoperative radiotherapy, is not well selected on the basis of NICE 2020 criteria and is better identified with proven MRI prognostic factors (extramural venous invasion, tumour deposits, and circumferential resection margin). FUNDING: None

Combined Spatial Prediction of Schistosomiasis and Soil-Transmitted Helminthiasis in Sierra Leone: A Tool for Integrated Disease Control

Two forms of schistosomiasis or bilharzia (intestinal and urogenital) exist in Sierra Leone. The main control strategy for this disease currently is through mass drug administration (MDA) according to the World Health Organization recommended anthelminthic chemotherapy guidelines, and others include snail control, behavior change, and safe water, sanitation and hygiene. Survey on distribution and prevalence of the disease is vital to the planning of MDA in each district. The distribution of intestinal schistosomiasis in the country has been reported previously. The current national survey showed that urogenital schistosomiasis has a specific focal distribution particularly in the central and eastern regions of the country, most prevalent in Bo (24.6%), Koinadugu (20.4%) and Kono (25.3%) districts. Using a simple probabilistic model, this map was combined with the previously reported maps on intestinal schistosomiasis and the combined schistosomiasis prevalence was estimated. The combined schistosomiasis map highlights the presence of high-risk communities in an extensive area in the northeastern half of the country, which provides a tool for planning the national MDA activities

Genetic control of Eucalyptus urophylla and E. grandis resistance to canker caused by Chrysoporthe cubensis

Chrysophorte cubensis induced canker occurs in nearly all tropical and subtropical regions where eucalypts are planted, causing losses in both wood quality and volume productivity, especially so in the warmer and more humid regions of Brazil. The wide inter and intra-specific genetic variability of resistance to canker among Eucalyptus species facilitates the selection of resistant plants. In this study, we evaluated resistance to this pathogen in five Eucalyptus grandis (G) and 15 E. urophylla (U) trees, as well as in 495 individuals from 27 progenies derived from crosses between the trees. In the field, six-months-old test seedlings were inoculated with C. cubensis. Lesion length in the xylem and bark was measured eight months later. The results demonstrated that xylem lesions could preferentially be used for the selection of resistant clones. Eight trees (7 U and 1 G) were susceptible, and the remainder (8 U and 4 G) resistant. Individual narrow and broad sense heritability estimates were 17 and 81%, respectively, thereby suggesting that canker resistance is quantitative and highly dependent on dominance and epistasis

Methodological considerations in the analysis of fecal glucocorticoid metabolites in tufted capuchins (Cebus apella)

Analysis of fecal glucocorticoid (GC) metabolites has recently become the standard method to monitor adrenocortical activity in primates noninvasively. However, given variation in the production, metabolism, and excretion of GCs across species and even between sexes, there are no standard methods that are universally applicable. In particular, it is important to validate assays intended to measure GC production, test extraction and storage procedures, and consider the time course of GC metabolite excretion relative to the production and circulation of the native hormones. This study examines these four methodological aspects of fecal GC metabolite analysis in tufted capuchins (Cebus apella). Specifically, we conducted an adrenocorticotrophic hormone (ACTH) challenge on one male and one female capuchin to test the validity of four GC enzyme immunoassays (EIAs) and document the time course characterizing GC me- tabolite excretion in this species. In addition, we compare a common field-friendly technique for extracting fecal GC metabolites to an established laboratory extraction methodology and test for effects of storing “field extracts” for up to 1 yr. Results suggest that a corticosterone EIA is most sensitive to changes in GC production, provides reliable measures when extracted according to the field method, and measures GC metabolites which remain highly stable after even 12 mo of storage. Further, the time course of GC metabolite excretion is shorter than that described yet for any primate taxa. These results provide guidelines for studies of GCs in tufted capuchins, and underscore the importance of validating methods for fecal hormone analysis for each species of interest

Improved mapping strategy to better inform policy on the control of schistosomiasis and soil-transmitted helminthiasis in Sierra Leone

<p>Abstract</p> <p>Background</p> <p>Schistosomiasis and soil-transmitted helminthiasis (STH) are endemic in Sierra Leone confirmed by national mapping in 2008. To better inform planning of preventive chemotherapy strategy, another survey was conducted before mass drug administration (MDA) in seven districts according to the mapping results or local knowledge. Fifty-nine chiefdoms and one school in every chiefdom were selected. Thirty school children aged 9-14 years from each school (total: 1760) were examined by parasitological methods for infection with <it>Schistosoma mansoni </it>and STHs.</p> <p>Results</p> <p>The overall prevalence of <it>S. mansoni </it>was 40.2% (95% confidence interval (CI): 37.9-42.5%), particularly in Kailahun (63.3%), Kenema (46.7%), Koinadugu (41.9%) and Kono (71.7%). The results demonstrated the focal distribution of <it>S. mansoni </it>in Bo, Tonkolili and Bombali districts with prevalence ranging from 0.0-63.3%, 3.3-90.0% and 0.0-67.9% respectively. The arithmetic mean intensity of <it>S. mansoni </it>infection was 95.4 epg (95% CI: 61.4-129.5 epg), Heavy mean intensity of infection was found in Kailahun (120.2 epg), Kenema (104.5 epg), Koinadugu (112.3 epg) and Kono (250.3 epg). Heavy or moderate infection with <it>S. mansoni </it>occurred in 20.7% of children examined. Hookworm prevalence was moderate: 31.2% (95% CI: 29.1-33.4%), but high in Bo (50.0%) and Tonkolili (56.7%). Hookworm intensity of infection was light with a mean epg of 53.0 (95% CI: 38.4-67.7 epg). Prevalence and intensity of <it>Ascaris lumbricoides </it>(1.5%, 17.8 epg) and <it>Trichuris trichiura </it>(2.5%, 20.3 epg) was low.</p> <p>Conclusions</p> <p>The prediction by previous spatial analysis that <it>S. mansoni </it>was highly endemic across north-eastern Sierra Leone was confirmed with a significant proportion of children heavily or moderately infected. The distribution of <it>S. mansoni </it>in Bo, Tonkolili and Bombali districts ranged widely, highlighting the importance of considering the nature of focal transmission in national mapping exercises. These results were used to refine the MDA for schistosomiasis control to chiefdom implementation units rather than the entire district in these 3 districts. The survey demonstrated that sufficient number of survey sites for schistosomiasis mapping in each district should be used to provide a better national planning of MDA activities, and that it is affordable with the contributions from all parties involved and national resources mobilized.</p

Identification of the Bovine Arachnomelia Mutation by Massively Parallel Sequencing Implicates Sulfite Oxidase (SUOX) in Bone Development

Arachnomelia is a monogenic recessive defect of skeletal development in cattle. The causative mutation was previously mapped to a ∼7 Mb interval on chromosome 5. Here we show that array-based sequence capture and massively parallel sequencing technology, combined with the typical family structure in livestock populations, facilitates the identification of the causative mutation. We re-sequenced the entire critical interval in a healthy partially inbred cow carrying one copy of the critical chromosome segment in its ancestral state and one copy of the same segment with the arachnomelia mutation, and we detected a single heterozygous position. The genetic makeup of several partially inbred cattle provides extremely strong support for the causality of this mutation. The mutation represents a single base insertion leading to a premature stop codon in the coding sequence of the SUOX gene and is perfectly associated with the arachnomelia phenotype. Our findings suggest an important role for sulfite oxidase in bone development

Which clustering algorithm is better for predicting protein complexes?

<p>Abstract</p> <p>Background</p> <p>Protein-Protein interactions (PPI) play a key role in determining the outcome of most cellular processes. The correct identification and characterization of protein interactions and the networks, which they comprise, is critical for understanding the molecular mechanisms within the cell. Large-scale techniques such as pull down assays and tandem affinity purification are used in order to detect protein interactions in an organism. Today, relatively new high-throughput methods like yeast two hybrid, mass spectrometry, microarrays, and phage display are also used to reveal protein interaction networks.</p> <p>Results</p> <p>In this paper we evaluated four different clustering algorithms using six different interaction datasets. We parameterized the MCL, Spectral, RNSC and Affinity Propagation algorithms and applied them to six PPI datasets produced experimentally by Yeast 2 Hybrid (Y2H) and Tandem Affinity Purification (TAP) methods. The predicted clusters, so called protein complexes, were then compared and benchmarked with already known complexes stored in published databases.</p> <p>Conclusions</p> <p>While results may differ upon parameterization, the MCL and RNSC algorithms seem to be more promising and more accurate at predicting PPI complexes. Moreover, they predict more complexes than other reviewed algorithms in absolute numbers. On the other hand the spectral clustering algorithm achieves the highest valid prediction rate in our experiments. However, it is nearly always outperformed by both RNSC and MCL in terms of the geometrical accuracy while it generates the fewest valid clusters than any other reviewed algorithm. This article demonstrates various metrics to evaluate the accuracy of such predictions as they are presented in the text below. Supplementary material can be found at: <url>http://www.bioacademy.gr/bioinformatics/projects/ppireview.htm</url></p