| 1. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 2. |
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| 3. |
- Drake, TM, et al.
(författare)
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Surgical site infection after gastrointestinal surgery in children: an international, multicentre, prospective cohort study
- 2020
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Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings.MethodsA multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI).ResultsOf 1159 children across 181 hospitals in 51 countries, 523 (45·1%) children were from high HDI, 397 (34·2%) from middle HDI and 239 (20·6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12·8% (51/397) in middle HDI and 24·7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI.ConclusionThe odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.
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| 4. |
- Abazov, V. M., et al.
(författare)
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The upgraded DO detector
- 2006
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 565:2, s. 463-537
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Tidskriftsartikel (refereegranskat)abstract
- The DO experiment enjoyed a very successful data-collection run at the Fermilab Tevatron collider between 1992 and 1996. Since then, the detector has been upgraded to take advantage of improvements to the Tevatron and to enhance its physics capabilities. We describe the new elements of the detector, including the silicon microstrip tracker, central fiber tracker, solenoidal magnet, preshower detectors, forward muon detector, and forward proton detector. The uranium/liquid -argon calorimeters and central muon detector, remaining from Run 1, are discussed briefly. We also present the associated electronics, triggering, and data acquisition systems, along with the design and implementation of software specific to DO.
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| 5. |
- Algaba, Juan-Carlos, et al.
(författare)
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Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign
- 2021
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 911:1
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Forskningsöversikt (refereegranskat)abstract
- In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M o˙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87's spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded.
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| 6. |
- Bairy, Sneha, et al.
(författare)
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Automation aided optimization of cloning, expression and purification of enzymes of the bacterial sialic acid catabolic and sialylation pathways enzymes for structural studies.
- 2018
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Ingår i: Microbial biotechnology. - : Wiley. - 1751-7915. ; 11:2, s. 420-428
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Tidskriftsartikel (refereegranskat)abstract
- The process of obtaining a well-expressing, soluble and correctly folded constructs can be made easier and quicker by automating the optimization of cloning, expression and purification. While there are many semiautomated pipelines available for cloning, expression and purification, there is hardly any pipeline that involves complete automation. Here, we achieve complete automation of all the steps involved in cloning and invivo expression screening. This is demonstrated using 18 genes involved in sialic acid catabolism and the surface sialylation pathway. Our main objective was to clone these genes into a His-tagged Gateway vector, followed by their small-scale expression optimization invivo. The constructs that showed best soluble expression were then selected for purification studies and scaled up for crystallization studies. Our technique allowed us to quickly find conditions for producing significant quantities of soluble proteins in Escherichia coli, their large-scale purification and successful crystallization of a number of these proteins. The method can be implemented in other cases where one needs to screen a large number of constructs, clones and expression vectors for successful recombinant production of functional proteins.
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| 7. |
- Barra, Sérgio, et al.
(författare)
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Very long-term survival and late sudden cardiac death in cardiac resynchronization therapy patients
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 40:26, s. 2121-2127
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The very long-term outcome of patients who survive the first few years after receiving cardiac resynchronization therapy (CRT) has not been well described thus far. We aimed to provide long-term outcomes, especially with regard to the occurrence of sudden cardiac death (SCD), in CRT patients without (CRT-P) and with defibrillator (CRT-D).METHODS AND RESULTS: A total of 1775 patients, with ischaemic or non-ischaemic dilated cardiomyopathy, who were alive 5 years after CRT implantation, were enrolled in this multicentre European observational cohort study. Overall long-term mortality rates and specific causes of death were assessed, with a focus on late SCD. Over a mean follow-up of 30 months (interquartile range 10-42 months) beyond the first 5 years, we observed 473 deaths. The annual age-standardized mortality rates of CRT-D and CRT-P patients were 40.4 [95% confidence interval (CI) 35.3-45.5] and 97.2 (95% CI 85.5-109.9) per 1000 patient-years, respectively. The adjusted hazard ratio (HR) for all-cause mortality was 0.99 (95% CI 0.79-1.22). Twenty-nine patients in total died of late SCD (14 with CRT-P, 15 with CRT-D), corresponding to 6.1% of all causes of death in both device groups. Specific annual SCD rates were 8.5 and 5.8 per 1000 patient-years in CRT-P and CRT-D patients, respectively, with no significant difference between groups (adjusted HR 1.0, 95% CI 0.45-2.44). Death due to progressive heart failure represented the principal cause of death (42.8% in CRT-P patients and 52.6% among CRT-D recipients), whereas approximately one-third of deaths in both device groups were due to non-cardiovascular death.CONCLUSION: In this first description of very long-term outcomes among CRT recipients, progressive heart failure death still represented the most frequent cause of death in patients surviving the first 5 years after CRT implant. In contrast, SCD represents a very low proportion of late mortality irrespective of the presence of a defibrillator.
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| 9. |
- Narayanan, Sampath Kumar
(författare)
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A multifactorial approach to targeting signalling pathways in diabetic foot ulcers
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Diabetic foot ulcers (DFU) are one of the most debilitating complication of diabetes that adversely impacts the health, economics and quality of life of the afflicted individual. The primary pathogenic factor of DFU is hyperglycemia, and its negative effects on normal signaling pathways is still being investigated. As such, there is no specific therapy that could target the underlying dysregulations caused by hyperglycemia. So, it is important to delve into various pathways that are altered by hyperglycemia in diabetic foot in order to successfully establish novel treatment paradigms. Wound healing consists of various phases where different cellular processes such as cell proliferation, migration, angiogenesis and apoptosis coordinate to achieve a swift healing of the wound. In my thesis, I have investigated several signaling pathways that play key roles in wound healing and are profoundly disturbed by hyperglycemia in diabetes. Notch signaling pathway is an important pathway where receptors and ligands from juxtaposed cells activate signal transduction. Upon activation, an intracellular domain of Notch (NICD) translocates to the nucleus and initiates the transcription of specific targets to control cell proliferation, cell migration, angiogenesis, differentiation and apoptosis. In paper-I, we show that Notch1 is activated in human and rodent skin and several processes central to wound healing are impaired in response to hyperglycemia in a Notch1 dependent manner. Mechanistically, we show that hyperglycemia activates a Dll4-Notch1 feedforward loop that impairs wound healing in diabetes. Inhibition of Notch signaling by chemical and genetic approaches improved wound healing in diabetic mice significantly. IGF-I is a growth hormone that is expressed in every cell of our body. The circulating IGF-I is however derived mainly from the liver. IGF-I promotes wound healing and its levels are decreased in diabetic wounds. However, the contribution of circulating IGF-I to wound healing is unknown. In Paper II, we generated a liver-specific IGF-I knockout mice and induced diabetes in these mice to study the effect of liver-derived IGF-I on wound healing. We found that the lack of liver-derived IGF-I did not affect healthy wound healing. Although diabetes delayed wound healing, there was no difference between knock-out mice and control mice. In addition, the processes contributing to wound healing were not altered by the liver-derived IGF-I deficiency. In summary, we found that a lack of liver-derived IGF-I did not affect wound healing. Future therapies using IGF-I can be designed to be delivered locally since systemic IGF-I therapy is known to carry risks of unfavorable side-effects. In papers-III and IV, I have investigated the roles of miRNA-210 and miRNA-34a in diabetic wound healing respectively. miR-210 is induced by transcription factor HIF-1 in response to hypoxia. miR-210 mirrors HIF function in hypoxia by regulating important processes such as cell proliferation, migration, apoptosis, metabolism and angiogenesis. We found that miR-210 expression is reduced in diabetic wounds and locally reconstituting miR-210 using mimics improves diabetic wound healing significantly. miR-210 reconstitution led to a reduction in the oxygen consumption rate in the wounds that led to a decrease in ROS levels in the wound tissue. This metabolic reprogramming by miR-210 ultimately resulted in the improvement in different cellular processes central to wound healing. miR-34a plays important roles in cell cycle and DNA repair. Importantly, miR-34a has been shown to regulate Notch1 directly. Although there are contrasting reports on their function in hypoxia and diabetes, their role in diabetic wound healing has not been elucidated. In paper-IV, we show that miR-34a was reduced in DFUs and in the wounds of diabetic mice. We also found that a long exposure to hypoxia increased miR-34a expression exclusively in keratinocytes but exposing cells to high glucose decreased its expression in hypoxia. Reciprocally, Notch1 expression levels increased in keratinocytes under hypoxic and high glucose levels in a time-dependent manner. Finally, we found that diabetic wounds injected with miR-34a mimic showed significantly lower expression of Notch1, directly correlating with paper-I, indicating that reconstitution of miR-34a could be a potential therapeutic strategy for diabetic wounds.
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