| 51. |
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| 52. |
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| 53. |
- Brandt, Patrik, et al.
(författare)
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System thinking on Risk Analysis
- 2004
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Ingår i: SABI 2004: Business Systems -- Environmental Contexts.
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Konferensbidrag (refereegranskat)abstract
- The word risk originates from the Italian word risicare which means to dare and from this point of view, risk is more of a choice than a fate. Risk is about the actions that we dare to take and these in turn depend on the freedom we have to make choices (Bernstein, 1998). It can also be defined as the possibility of harm or loss to any resource within an information system, which accentuate the importance of identifying the organisation's assets (Ramachandran, 2002).The obvious fact that information is one of the most important asset within a company, results in that it is necessary to try to predict the risks that exists against these and consequently also against the organisation's goals and visions. It is impossible to identify all potential risks but a very good tool for identifying as many as possible and then assigning them appropriate protective measures, is the risk analysis.Since many significant security processes are built upon risk analysis and also security planning, it is necessary that the analysis is accomplished in an accurate way. This meaning that factors in the inner and outer surrounding environment that could affect the final result also must be taken into consideration, e.g. different communication channels. Thus, a holistic perspective is necessary when performing a risk analysis but also when working with security issues in general.Today, security solutions are often focused on technology and not on the system as a whole (Schneier, 2000) and considering that development and use of technology has lead us to think in terms of systems, we mean that this should hold for the information security area as well. Also the fact that the concept of wholeness is very important in information security and that general system theory is a general science of wholeness (v. Bertalanffy, 1969), makes us wonder: what could be more suitable to apply on security issues?For that reason, we present some ideas for a modified risk analysis method in this paper, based upon an existing risk analysis used by the case study object The Corporation of Swedish Pharmacies, Apoteket AB. They has recently added two customer care centres to its organisation and as a result of this, also a number of communication channels that are integrated with different information sources that contains classified information, e.g. personal particulars. The ideas of a modified risk analysis could be used by customer care centre organisations using several communication channels. These ideas are influenced by general systems theory that has been combined with a method used to analyse information flows in organisations. We have studied the company's existing risk analysis method and in combination with qualitative data, e.g. interviews, we have some suggestions of a risk analysis that emphasises the holistic perspective and the relations between the different entities in the overall information system.The suggested ideas will be reviewed together with the department of IT-security at Apoteket AB and after that tested within the organisation. It is noticeable that like all work with information security, the suggested method is a cyclic process that constantly develops and undergoes changes in relation to its dynamic context. Results and feedback from this implementation will be presented in forthcoming papers during 2004.
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| 54. |
- Brem, Jürgen, et al.
(författare)
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Imitation of β-lactam binding enables broad-spectrum metallo-β-lactamase inhibitors
- 2022
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Ingår i: Nature Chemistry. - : Springer Nature. - 1755-4330 .- 1755-4349. ; 14:1, s. 15-24
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Tidskriftsartikel (refereegranskat)abstract
- Carbapenems are vital antibiotics, but their efficacy is increasingly compromised by metallo-β-lactamases (MBLs). Here we report the discovery and optimization of potent broad-spectrum MBL inhibitors. A high-throughput screen for NDM-1 inhibitors identified indole-2-carboxylates (InCs) as potential β-lactamase stable β-lactam mimics. Subsequent structure-activity relationship studies revealed InCs as a new class of potent MBL inhibitor, active against all MBL classes of major clinical relevance. Crystallographic studies revealed a binding mode of the InCs to MBLs that, in some regards, mimics that predicted for intact carbapenems, including with respect to maintenance of the Zn(II)-bound hydroxyl, and in other regards mimics binding observed in MBL-carbapenem product complexes. InCs restore carbapenem activity against multiple drug-resistant Gram-negative bacteria and have a low frequency of resistance. InCs also have a good in vivo safety profile, and when combined with meropenem show a strong in vivo efficacy in peritonitis and thigh mouse infection models.
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| 55. |
- De Rosa, Maria, et al.
(författare)
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Design, synthesis and in vitro biological evaluation of oligopeptides targeting E. coli type I signal peptidase (LepB)
- 2017
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 25:3, s. 897-911
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Tidskriftsartikel (refereegranskat)abstract
- Type I signal peptidases are potential targets for the development of new antibacterial agents. Here we report finding potent inhibitors of E. coli type I signal peptidase (LepB), by optimizing a previously reported hit compound, decanoyl-PTANA-CHO, through modifications at the N- and C-termini. Good improvements of inhibitory potency were obtained, with IC50s in the low nanomolar range. The best inhibitors also showed good antimicrobial activity, with MICs in the low μg/mL range for several bacterial species. The selection of resistant mutants provided strong support for LepB as the target of these compounds. The cytotoxicity and hemolytic profiles of these compounds are not optimal but the finding that minor structural changes cause the large effects on these properties suggests that there is potential for optimization in future studies.
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| 56. |
- Ekelund, A, et al.
(författare)
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Additional colloids have only a minor haemodilutive effect after surgery for aneurysmal subarachnoid haemorrhage
- 1999
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Ingår i: British Journal of Neurosurgery. - : Informa UK Limited. - 0268-8697 .- 1360-046X. ; 13:4, s. 399-404
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Tidskriftsartikel (refereegranskat)abstract
- Haemodilution is commonly used as prophylaxis, as well as treatment for cerebral ischaemia after aneurysmal subarachnoid haemorrhage (SAH). Thirty-six patients operated for aneurysmal SAH were evaluated retrospectively; 24 received haemodilutive therapy and 12 patients, as a control group, received no additional therapy. There was a 'spontaneous' drop in haematocrit by 22% in both groups, and a corresponding drop in haemoglobin by 23% in the treatment group and 19% in the non-haemodiluted group, during the first 4 days after the SAH. After the initial decrease the haematocrit remained stable between 0.28 and 0.33 until day 14 in both groups. The haemodilutive group had only a minor lower haematocrit level during days 8-12 as the additional fluid resulted in increased renal excretion. This minor difference was, however, significant (p < 0.02).
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| 57. |
- Ekelund, A, et al.
(författare)
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Effects of iso- and hypervolemic hemodilution on regional cerebral blood flow and oxygen delivery for patients with vasospasm after aneurysmal subarachnoid hemorrhage.
- 2002
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Ingår i: Acta Neurochirurgica. - : Springer Science and Business Media LLC. - 0001-6268. ; 144:7, s. 703-713
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Tidskriftsartikel (refereegranskat)abstract
- SUMMARY:BACKGROUND: Arterial vasospasm after subarachnoid hemorrhage may cause cerebral ischemia. Treatment with hemodilution, reducing blood viscosity, and hypervolemia, increasing cardiac performance and distending the vasospastic artery, are clinically established methods to improve blood flow through the vasospastic arterial bed.METHOD: Eight patients with transcranial Doppler verified vasospasm after subarachnoid hemorrhage were investigated with global (two-dimensional (133)Xenon) and regional (three-dimensional (99 m)Tc-HMPAO) cerebral blood flow (CBF) measurements, before and after 1/iso- and 2/hypervolemic hemodilution. Hematocrit was reduced to 0.28 from 0.36. Hypervolemia was achieved by increasing blood volume by 1100 ml.FINDINGS: Isovolemic hemodilution increased global cerebral blood flow from 52.25+/-10.12 to 58.56+/-11.73 ml * 100 g(-1) * min(-1) (p<0.05), but after hypervolemic hemodilution CBF returned to 51.38+/-11.34 ml * 100 g(-1) * min(-1). Global cerebral delivery rate of oxygen (CDRO(2)) decreased from 7.94+/-1.92 to 6.98+/-1.66 ml * 100 g(-1) * min(-1) (p<0.001) during isovolemic hemodilution and remained reduced, 6.77+/-1.60 ml * 100 g(-1) * min(-1) (p<0.001), after the hypervolemic hemodilution. As a test of the hemodilution effect on regional CDRO(2) an ischemic threshold was defined as the maximal amount of oxygen transported by a CBF of 10 ml * 100 g(-1) * min(-1) at a Hb 140 g/l which corresponds to a CDRO(2) of 1.83 ml * 100 g(-1) * min(-1). The brain volume with a CDRO(2) exceeding the ichemic threshold was 1300+/-236 ml before intervention. After isovolemic hemodilution the non-ischemic brain volume was reduced to 1206+/-341 (p<0,003). After hypervolemic hemodilution the non-ischemic brain volume remained reduced at 1228+/-347 ml (p<0.05).INTERPRETATION: The present study of controlled isovolemic hemodilution demonstrated increased global CBF, but there was a pronounced reduction in oxygen delivery capacity. Both CBF and CDRO(2) remained decreased during further hypervolemic hemodilution. We conclude that hemodilution to hematocrit 0.28 is not beneficial for patients with cerebral vasospasm after SAH.
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| 58. |
- Ekelund, A, et al.
(författare)
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Transcranial cerebral oximetry related to transcranial Doppler after aneurysmal subarachnoid haemorrhage
- 1998
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Ingår i: Acta Neurochirurgica. - : Springer Science and Business Media LLC. - 0001-6268 .- 0942-0940. ; 140:10, s. 1029-1036
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Tidskriftsartikel (refereegranskat)abstract
- Noninvasive methods for detecting cerebral artery vasospasm, still a serious complication following aneurysmal subarachnoid haemorrhage, are of vital interest. Up-to-date transcranial Doppler ultrasound (TCD) has proved to be sensitive in detecting vasospasm in the middle cerebral artery, but has less accuracy for other cerebral arteries. Transcranial cerebral oximetry (TCCO) is a new non-invasive technique which may increase the reliability for detecting cerebral ischaemia. The purpose of the present study was to evaluate a putative correlation between TCCO and TCD. We examined the two hemispheres in 14 patients with the aim of evaluating a proposed correlation between TCD and TCCO. Analysis of all absolute values (maximum TCD mFV and minimum TCCO saturation, respectively) in all series indicate a correlation between TCCO and TCD, p < 0.01, r = -0.62. All patients with TCD mean flow velocity > 120 cm/s also presented TCCO saturation < 60%. Conversely, all patients with normal TCCO saturation (> or = 63%) presented normal or moderately increased TCD velocities. In clinical neurosurgical practice it is of great interest if a true correlation between TCD and TCCO exists. The present results support the assumption that TCCO may enhance the reliability for detecting cerebral ischaemia after aneurysmal subarachnoid haemorrhage.
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| 59. |
- Fernström, Maria, 1960-, et al.
(författare)
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Improved Muscle Mitochondrial Capacity Following Gastric Bypass Surgery in Obese Subjects
- 2016
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Ingår i: Obesity Surgery. - New York, USA : Springer. - 0960-8923 .- 1708-0428. ; 26:7, s. 1391-1397
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Tidskriftsartikel (refereegranskat)abstract
- Background: Weight loss resulting from low-calorie diets is often less than expected. We hypothesized that energy restriction would influence proton leakage and improve mitochondrial efficiency, leading to reduced energy expenditure, partly explaining the difficulties in weight loss maintenance.Methods: Eleven women with a median BMI of 38.5 kg/m(2) (q-range 37-40), and referred to gastric bypass surgery participated. Before surgery, and at 6 months of follow-up, muscle biopsies were collected from the vastus lateralis muscle. Mitochondria were isolated and analyzed for coupled (state 3) and uncoupled (state 4) respiration and mitochondrial capacity (P/O ratio).Results: At follow-up, the participants had a median BMI of 29.6 kg/m(2) (28.3-32.0). State 3 increased from 20.6 (17.9-28.9) to 34.9 nmol O2/min/U citrate synthase (CS) (27.0-49.0), p = 0.01, while state 4 increased from 2.8 (1.8-4.2) to 4.2 nmol O2/min/U CS (3.1-6.1), although not statistically significant. The P/O ratio increased from 2.7 (2.5-2.8) to 3.2 (3.0-3.4), p = 0.02, indicating improved mitochondrial efficiency.Conclusions: Six months after gastric bypass surgery, the mitochondrial capacity for coupled, i.e., ATP-generating, respiration increased, and the P/O ratio improved. Uncoupled respiration was not enhanced to the same extent. This could partly explain the decreased basal metabolism and the reduced inclination for weight loss during energy restriction.
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| 60. |
- Gatherer, D., et al.
(författare)
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ICTV Virus Taxonomy Profile: Herpesviridae 2021
- 2021
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Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 102:10
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Forskningsöversikt (refereegranskat)abstract
- Members of the family Herpesviridae have enveloped, spherical virions with characteristic complex structures consisting of symmetrical and non-symmetrical components. The linear, double-stranded DNA genomes of 125-241 kbp contain 70-170 genes, of which 43 have been inherited from an ancestral herpesvirus. In general, herpesviruses have coevolved with and are highly adapted to their hosts, which comprise many mammalian, avian and reptilian species. Following primary infection, they are able to establish lifelong latent infection, during which there is limited viral gene expression. Severe disease is usually observed only in the foetus, the very young, the immunocompromised or following infection of an alternative host. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Herpesviridae, which is available at ictv.global/report/herpesviridae.
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