Candidates in Astroviruses, Seadornaviruses, Cytorhabdoviruses and Coronaviruses for +1 frame overlapping genes accessed by leaky scanning

<p>Abstract</p> <p>Background</p> <p>Overlapping genes are common in RNA viruses where they serve as a mechanism to optimize the coding potential of compact genomes. However, annotation of overlapping genes can be difficult using conventional gene-finding software. Recently we have been using a number of complementary approaches to systematically identify previously undetected overlapping genes in RNA virus genomes. In this article we gather together a number of promising candidate new overlapping genes that may be of interest to the community.</p> <p>Results</p> <p>Overlapping gene predictions are presented for the astroviruses, seadornaviruses, cytorhabdoviruses and coronaviruses (families <it>Astroviridae</it>, <it>Reoviridae</it>, <it>Rhabdoviridae </it>and <it>Coronaviridae</it>, respectively).</p

20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years

The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials

Background Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. Methods We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). Findings Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5–14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4–8·6]; rate ratio 1·37 [95% CI 1·17–1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92–1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95–1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94–1·15]; p=0·45). Interpretation Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered—eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Downstream sequences influence the choice between a naturally occurring noncanonical and closely positioned upstream canonical heptameric fusion motif during bovine coronavirus subgenomic mRNA synthesis

Mechanisms leading to subgenomic mRNA (sgmRNA) synthesis in coronaviruses are poorly understood but are known to involve a heptameric signaling motif, originally called the intergenic sequence. The intergenic sequence is the presumed crossover region (fusion site) for RNA-dependent RNA polymerase (RdRp) during discontinuous transcription, a process leading to sgmRNAs that are both 5 ' and 3 ' coterminal. In the bovine coronavirus, the major fusion site for synthesis of mRNA 5 (GGUAGAC) does not conform to the canonical motif (UC [U,C] AAAC) at three positions (underlined), yet it lies just 14 nucleotides downstream from such a sequence (UCCAAAC). The infrequently used canonical sequence, by computer prediction, is buried within the stem of a stable hairpin (-17.2 kcal/mol). Here we document the existence of this stem by enzyme probing and examine its influence and that of neighboring sequences on the unusual choice of fusion sites by analyzing transcripts made in vivo from mutated defective interfering RNA constructs. We learned that (i) mutations that were predicted to unfold the stem-loop in various ways did not switch RdRp crossover to the upstream canonical site, (ii) a totally nonconforming downstream motif resulted in no measurable transcription from either site, (iii) the canonical upstream site does not function ectopically to lend competence to the downstream noncanonical site, and (iv) altering flanking sequences downstream of the downstream noncanonical motif in ways that diminish sequence similarity with the virus genome 5 ' end caused a dramatic switch to the upstream canonical site. These results show that sequence elements downstream of the noneanonical site can dramatically influence the choice of fusion sites for synthesis of mRNA 5 and are interpreted as being most consistent with a mechanism of similarity-assisted RdRp strand switching during minus-strand synthesis

Contribution of the private sector healthcare service providers to malaria diagnosis in a prevention of re-introduction setting

Background: Sri Lanka is currently in the prevention of re-introduction phase of malaria. The engagement of the private sector health care institutions in malaria surveillance is important. The purpose of the study was to determine the number of diagnostic tests carried out, the number of positive cases identified and the referral system for diagnosis in the private sector and to estimate the costs involved. Methods: This prospective study of private sector laboratories within the Colombo District of Sri Lanka was carried out over a 6-month period in 2015. The management of registered private sector laboratories was contacted individually and the purpose of the study was explained. A reporting format was developed and introduced for monthly reporting. Results: Forty-one laboratories were eligible to be included in the study and 28 participated by reporting data on a monthly basis. Excluding blood bank samples and routine testing for foreign employment, malaria diagnostic tests were carried out on 973 individuals during the 6-month period and nine malaria cases were identified. In 2015, a total of 36 malaria cases were reported from Sri Lanka. Of these, 24 (67 %) were diagnosed in the Colombo District and 50 % of them were diagnosed in private hospitals. Conclusions: An equal number of cases were diagnosed from the private sector and government sector in the Colombo District in 2015. The private sector being a major contributor in the detection of imported malaria cases in the country should be actively engaged in the national malaria surveillance system

The risk of imported malaria in security forces personnel returning from overseas missions in the context of prevention of re-introduction of malaria to Sri Lanka

Background: Sri Lanka is a malaria-free country. However it remains surrounded by countries with endemic malaria transmission. Since the last indigenous case of malaria was reported in October 2012, only imported malaria cases have been diagnosed with 36 cases detected in 2015, which includes 17 cases each of Plasmodium vivax and Plasmodium falciparum and two cases of Plasmodium ovale. Methods: This study investigated the knowledge and practices regarding malaria chemoprophylaxis among all the Sri Lankan security forces personnel returning from peacekeeping missions in malaria endemic countries over a 7 month period. Adherence to other malaria prevention measures, occurrence of adverse events and incident cases of malaria were also recorded maintaining the anonymity of the respondents. Potential associations for non-compliance were studied. Results: Interviews were carried out with 559 security forces personnel returning home from foreign deployments in malaria-endemic regions (males: 550, 98.4 %). The majority (553, 98.9 %) was well aware of the need for chemoprophylaxis during the overseas stay and its regular use as prescribed. The overall adherence to chemoprophylaxis was good with 78.7 % (440/559) reporting regular, as prescribed, use. Having better educational qualifications, being female, being prescribed mefloquine, having fever during deployment and belonging to a security force other than the army were significantly associated with poor compliance (p < 0.05). Conclusions: The study reveals that knowledge regarding malaria chemoprophylaxis among Sri Lankan security forces personnel serving abroad was good, a fact that may have contributed to absence/extremely low incidence of malaria during deployment

Hydrogenation of CO2 to Methanol on CeOx/Cu(111) and ZnO/Cu(111) Catalysts: Role of the Metal-Oxide Interface and Importance of Ce3+ Sites

© 2016 American Chemical Society. The role of the interface between a metal and oxide (CeOx-Cu and ZnO-Cu) is critical to the production of methanol through the hydrogenation of CO2 (CO2 + 3H2 → CH3OH + H2O). The deposition of nanoparticles of CeOx or ZnO on Cu(111),oxi &lt; 0.3 monolayer, produces highly active catalysts for methanol synthesis. The catalytic activity of these systems increases in the sequence: Cu(111) &lt; ZnO/Cu(111) &lt; CeOx/Cu(111). The apparent activation energy for the CO2 → CH3OH conversion decreases from 25 kcal/mol on Cu(111) to 16 kcal/mol on ZnO/Cu(111) and 13 kcal/mol on CeOx/Cu(111). The surface chemistry of the highly active CeOx-Cu(111) interface was investigated using ambient pressure X-ray photoemission spectroscopy (AP-XPS) and infrared reflection absorption spectroscopy (AP-IRRAS). Both techniques point to the formation of formates (HCOO-) and carboxylates (CO2δ-) during the reaction. Our results show an active state of the catalyst rich in Ce3+ sites which stabilize a CO2δ- species that is an essential intermediate for the production of methanol. The inverse oxide/metal configuration favors strong metal-oxide interactions and makes possible reaction channels not seen in conventional metal/oxide catalysts

Hydrogenation of CO2 to Methanol on CeOx/Cu(111) and ZnO/Cu(111) Catalysts: Role of the Metal-Oxide Interface and Importance of Ce3+ Sites

The role of the interface between a metal and oxide (CeOx-Cu and ZnO-Cu) is critical to the production of methanol through the hydrogenation of CO2 (CO2 + 3H2 → CH3OH + H2O). The deposition of nanoparticles of CeOx or ZnO on Cu(111),oxi &lt; 0.3 monolayer, produces highly active catalysts for methanol synthesis. The catalytic activity of these systems increases in the sequence: Cu(111) &lt; ZnO/Cu(111) &lt; CeOx/Cu(111). The apparent activation energy for the CO2 → CH3OH conversion decreases from 25 kcal/mol on Cu(111) to 16 kcal/mol on ZnO/Cu(111) and 13 kcal/mol on CeOx/Cu(111). The surface chemistry of the highly active CeOx-Cu(111) interface was investigated using ambient pressure X-ray photoemission spectroscopy (AP-XPS) and infrared reflection absorption spectroscopy (AP-IRRAS). Both techniques point to the formation of formates (HCOO-) and carboxylates (CO2δ-) during the reaction. Our results show an active state of the catalyst rich in Ce3+ sites which stabilize a CO2δ- species that is an essential intermediate for the production of methanol. The inverse oxide/metal configuration favors strong metal-oxide interactions and makes possible reaction channels not seen in conventional metal/oxide catalysts