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Sökning: WFRF:(Hofmann A.) > Forskningsöversikt

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1.
  • Algaba, Juan-Carlos, et al. (författare)
  • Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign
  • 2021
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 911:1
  • 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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2.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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3.
  • Aharonian, F., et al. (författare)
  • Simultaneous multiwavelength observations of the second exceptional gamma-ray flare of PKS2155-304 in July 2006
  • 2009
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 502:3, s. 749-770
  • Forskningsöversikt (refereegranskat)abstract
    • Aims. The X-ray-TeV connection and the evolution of the emitting particle population is studied in high-energy peaked BL Lac objects, by obtaining spectral information in both bands on sub-hour timescales. Methods. Simultaneous observations with HESS, Chandra and the Bronberg optical observatory were performed on the BL Lac object PKS 2155-304 in the night of July 29-30 2006, when the source underwent a major gamma-ray outburst during its high-activity state of Summer 2006. This event took place about 44 h after the other major outburst of the night of July 27-28, which is known for its ultrafast variability. An unprecedented 6 to 8 h of simultaneous, uninterrupted coverage was achieved, with spectra and light curves measured down to 7 and 2 min timescales, respectively. Results. The source exhibited one major flare along the night, at high energies. The gamma-ray flux reached a maximum of similar to 11 times the Crab flux (>400 GeV), with rise/decay timescales of similar to 1 h, plus a few smaller-amplitude flares superimposed on the decaying phase. The emission in the X-ray and VHE gamma-ray bands is strongly correlated, with no evidence of lags. The spectra also evolve with similar patterns, and are always soft ( photon index G > 2), indicating no strong shift of the peaks in the spectral energy distribution towards higher energies. Only at the flare maximum is there evidence that the gamma-ray peak is inside the observed passband, at similar to 400-600 GeV. The VHE spectrum shows a curvature that is variable with time and stronger at higher fluxes. The huge VHE variations (similar to 22x) are only accompanied by small-amplitude X-ray and optical variations (factor 2 and 15% respectively). The source has shown for the first time in a high-energy peaked BL Lac object a large Compton dominance (L(C)/L(S) similar to 10) - rapidly evolving - and a cubic relation between VHE and X-ray flux variations, during a decaying phase. These results challenge the common scenarios for the TeV-blazar emission.
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4.
  • Lardas, Michael, et al. (författare)
  • Systematic Review of Surgical Management of Nonmetastatic Renal Cell Carcinoma with Vena Caval Thrombus
  • 2016
  • Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 70:2, s. 265-280
  • Forskningsöversikt (refereegranskat)abstract
    • CONTEXT: Overall, 4-10% of patients with renal cell carcinoma (RCC) present with venous tumour thrombus. It is uncertain which surgical technique is best for these patients. Appraisal of outcomes with differing techniques would guide practice.OBJECTIVE: To systematically review relevant literature comparing the outcomes of different surgical therapies and approaches in treating vena caval thrombus (VCT) from nonmetastatic RCC.EVIDENCE ACQUISITION: Relevant databases (Medline, Embase, and the Cochrane Library) were searched to identify relevant comparative studies. Risk of bias and confounding assessments were performed. A narrative synthesis of the evidence was presented.EVIDENCE SYNTHESIS: The literature search identified 824 articles. Fourteen studies reporting on 2262 patients were included. No distinct surgical method was superior for the excision of VCT, although the method appeared to be dependent on tumour thrombus level. Minimal access techniques appeared to have better perioperative and recovery outcomes than traditional median sternotomy, but the impact on oncologic outcomes is unknown. Preoperative renal artery embolisation did not offer any oncologic benefits and instead resulted in significantly worse perioperative and recovery outcomes, including possibly higher perioperative mortality. The comparison of cardiopulmonary bypass versus no cardiopulmonary bypass showed no differences in oncologic outcomes. Overall, there were high risks of bias and confounding.CONCLUSIONS: The evidence base, although derived from retrospective case series and complemented by expert opinion, suggests that patients with nonmetastatic RCC and VCT and acceptable performance status should be considered for surgical intervention. Despite a robust review, the findings were associated with uncertainty due to the poor quality of primary studies available. The most efficacious surgical technique remains unclear.PATIENT SUMMARY: We examined the literature on the benefits of surgery to remove kidney cancers that have spread to neighbouring veins. The results suggest such surgery, although challenging and associated with high risk of complications, appears to be feasible and effective and should be contemplated for suitable patients if possible; however, many uncertainties remain due to the poor quality of the data.
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5.
  • Marconi, Lorenzo, et al. (författare)
  • Systematic Review and Meta-analysis of Diagnostic Accuracy of Percutaneous Renal Tumour Biopsy
  • 2016
  • Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 69:4, s. 660-673
  • Forskningsöversikt (refereegranskat)abstract
    • Context: The role of percutaneous renal tumour biopsy (RTB) remains controversial due to uncertainties regarding its diagnostic accuracy and safety.Objective: We performed a systematic review and meta-analysis to determine the safety and accuracy of percutaneous RTB for the diagnosis of malignancy, histologic tumour subtype, and grade.Evidence acquisition: Medline, Embase, and Cochrane Library were searched for studies providing data on diagnostic accuracy and complications of percutaneous core biopsy (CB) or fine-needle aspiration (FNA) of renal tumours. A meta-analysis was performed to obtain pooled estimates of sensitivity and specificity for diagnosis of malignancy. The Cohen kappa coefficient (κ) was estimated for the analysis of histotype/grade concordance between diagnosis on RTB and surgical specimen. Risk of bias assessment was performed (QUADAS-2).Evidence synthesis: A total of 57 studies recruiting 5228 patients were included. The overall median diagnostic rate of RTB was 92%. The sensitivity and specificity of diagnostic CBs and FNAs were 99.1% and 99.7%, and 93.2% and 89.8%, respectively. A good (κ = 0.683) and a fair (κ = 0.34) agreement were observed between histologic subtype and Fuhrman grade on RTB and surgical specimen, respectively. A very low rate of Clavien ≥2 complications was reported. Study limitations included selection and differential-verification bias.Conclusions: RTB is safe and has a high diagnostic yield in experienced centres. Both CB and FNA have good accuracy for the diagnosis of malignancy and histologic subtype, with better performance for CB. The accuracy for Fuhrman grade is fair. Overall, the quality of the evidence was moderate. Prospective cohort studies recruiting consecutive patients and using homogeneous reference standards are required.Patient summary: We systematically reviewed the literature to assess the safety and diagnostic performance of renal tumour biopsy (RTB). The results suggest that RTB has good accuracy in diagnosing renal cancer and its subtypes, and it appears to be safe. However, the quality of evidence was moderate, and better quality studies are required to provide a more definitive answer.
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6.
  • Abu-Ghanem, Yasmin, et al. (författare)
  • Limitations of Available Studies Prevent Reliable Comparison Between Tumour Ablation and Partial Nephrectomy for Patients with Localised Renal Masses : A Systematic Review from the European Association of Urology Renal Cell Cancer Guideline Panel
  • 2020
  • Ingår i: European Urology Oncology. - : Elsevier. - 2588-9311. ; 3:4, s. 423-442
  • Forskningsöversikt (refereegranskat)abstract
    • The European Association of Urology (EAU) Renal Cell Carcinoma (RCC) Guideline Panel performed a protocol-driven systematic review (SR) on thermal ablation (TA) compared with partial nephrectomy (PN) for T1N0M0 renal masses, in order to provide evidence to support its recommendations. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed, and only comparative studies published between 2000 and 2019 were included. Twenty-six nonrandomised comparative studies were included, recruiting a total of 167 80 patients. Risk of bias (RoB) assessment revealed high or uncertain RoB across all studies, with the vast majority being retrospective, observational studies with poorly matched controls and short follow-up. Limited data showed TA to be safe, but its long-term oncological effectiveness compared with PN remains uncertain. A quality assessment of pre-existing SRs (n = 11) on the topic, using AMSTAR, revealed that all SRs had low confidence rating, with all but two SRs being rated critically low. In conclusion, the current data are inadequate to make any strong and clear conclusions regarding the clinical effectiveness of TA for treating T1N0M0 renal masses compared with PN. Therefore, TA may be cautiously considered an alternative to PN for T1N0M0 renal masses, but patients must be counselled carefully regarding the prevailing uncertainties. We recommend specific steps to improve the evidence base based on robust primary and secondary studies.Patient summary: In this report, we looked at the literature to determine the effectiveness of thermoablation (TA) in the treatment of small kidney tumours compared with surgical removal. We found that TA could cautiously be offered as an option due to many remaining uncertainties regarding its effectiveness.
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7.
  • Fernández-Pello, Sergio, et al. (författare)
  • A Systematic Review and Meta-analysis Comparing the Effectiveness and Adverse Effects of Different Systemic Treatments for Non-clear Cell Renal Cell Carcinoma
  • 2017
  • Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 71:3, s. 426-436
  • Forskningsöversikt (refereegranskat)abstract
    • Context While vascular endothelial growth factor-targeted therapy and mammalian target of rapamycin inhibition are effective strategies in treating clear cell renal cell carcinoma (ccRCC), the most effective therapeutic approach for patients with non-clear cell RCC (non-ccRCC) is unknown. Objective To systematically review relevant literature comparing the oncological outcomes and adverse events of different systemic therapies for patients with metastatic non-ccRCC. Evidence acquisition Relevant databases including MEDLINE, Embase, and the Cochrane Library were searched up to March 24, 2016. Only comparative studies were included. Risk of bias and confounding assessments were performed. A meta-analysis was planned for and only performed if methodologically appropriate; otherwise, a narrative synthesis was undertaken. Evidence synthesis The literature search identified 812 potential titles and abstracts. Five randomized controlled trials, recruiting a total of 365 patients, were included. Three studies compared sunitinib against everolimus, one of which reported the results for non-ccRCC as a subgroup rather than as an entire randomized cohort. Individually, the studies showed a trend towards favoring sunitinib in terms of overall survival and progression-free survival (PFS; Everolimus versus Sunitinib in Patients with Metastatic Non-clear Cell Renal Cell Carcinoma hazard ratio [HR]: 1.41, 80% confidence interval [CI] 1.03–1.92 and 1.41, 95% CI: 0.88–2.27, Evaluation in Metastatic Non-clear Cell Renal Cell Carcinoma HR: 1.16, 95% CI: 0.67–2.01, Efficacy and Safety Comparison of RAD001 Versus Sunitinib in the First-line and Second-line Treatment of Patients with Metastatic Renal Cell Carcinoma HR: 1.5, 95% CI: 0.9–2.8), but this trend did not reach statistical significance in any study. Meta-analysis was performed on two studies which solely recruited patients with non-ccRCC reporting on PFS, the results of which were inconclusive (HR: 1.30, 95% CI: 0.91–1.86). Sunitinib was associated with more Grade 3–4 adverse events than everolimus, although this was not statistically significant. Conclusions This systematic review and meta-analysis represent a robust summary of the evidence base for systemic treatment of metastatic non-ccRCC. The results show a trend towards favoring vascular endothelial growth factor-targeted therapy for PFS and overall survival compared with mammalian target of rapamycin inhibitors, although statistical significance was not reached. The relative benefits and harms of these treatments remain uncertain. Further research, either in the form of an individual patient data meta-analysis involving all relevant trials, or a randomized controlled trial with sufficient power to detect potential differences between treatments, is needed. Patient summary We examined the literature to determine the most effective treatments for advanced kidney cancer patients whose tumors are not of the clear cell subtype. The results suggest that a drug called sunitinib might be more effective than everolimus, but the statistics supporting this statement are not yet entirely reliable. Further research is required to clarify this unmet medical need.
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8.
  • Fernández-Pello, Sergio, et al. (författare)
  • Management of Sporadic Renal Angiomyolipomas : A Systematic Review of Available Evidence to Guide Recommendations from the European Association of Urology Renal Cell Carcinoma Guidelines Panel
  • 2020
  • Ingår i: European Urology Oncology. - : Elsevier. - 2588-9311. ; 3:1, s. 57-72
  • Forskningsöversikt (refereegranskat)abstract
    • Context: Little is known about the natural history of sporadic angiomyolipomas (AMLs); there is uncertainty regarding the indications of treatment and treatment options. Objective: To evaluate the indications, effectiveness, harms, and follow-up of different management modalities for sporadic AML to provide guidance for clinical practice. Evidence acquisition: A systematic review of the literature was undertaken, incorporating Medline, Embase, and the Cochrane Library (from 1 January 1990 to 30 June 2017), in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. No restriction on study design was imposed. Patients with sporadic AML were included. The main interventions included active surveillance, surgery (nephron-sparing surgery and radical nephrectomy), selective arterial embolisation, and percutaneous or laparoscopic thermal ablations (radiofrequency, microwaves, or cryoablation). The outcomes included indications for active treatment, AML growth rate, AML recurrence rate, risk of bleeding, post-treatment renal function, adverse events of treatments, and modalities of followup. Risk of bias assessment was performed using standard Cochrane methods. Evidence synthesis: Among 2704 articles identified, 43 were eligible for inclusion (zero randomised controlled trials, nine nonrandomised comparative retrospective studies, and 34 single-arm case series). Most studies were retrospective and uncontrolled, and had a moderate to high risk of bias. Conclusions: In active surveillance series, spontaneous bleeding was reported in 2% of patients and active treatment was undertaken in 5%. Active surveillance is the most chosen option in 48% of the cases, followed by surgery in 31% and selective arterial embolisation in 17% of the cases. Selective arterial embolisation appeared to reduce AML volume but required secondary treatment in 30% of the cases. Surgery (particularly nephron-sparing surgery) was the most effective treatment in terms of recurrence and need for secondary procedures. Thermal ablation was an infrequent option. The association between AML size and the risk of bleeding remained unclear; as such the traditional 4-cm cut-off should not per se trigger active treatment. In spite of the limitations and uncertainties relating to the evidence base, the findings may be used to guide and inform clinical practice, until more robust data emerge. Patient summary: Sporadic angiomyolipoma (AML) is a benign tumour of the kidney consisting of a mixture of blood vessels, fat, and muscle. Large tumours may have a risk of spontaneous bleeding. However, the size beyond which these tumours need to be treated remains unclear. Most small AMLs can be monitored without any active treatment. For those who need treatment, options include surgical removal of the tumour or stopping its blood supply (selective embolisation). Surgery has a lower recurrence rate and lower need for a repeat surgical procedure.
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9.
  • Filler, G, et al. (författare)
  • Cystatin C as a marker of GFR - history, indications, and future research
  • 2005
  • Ingår i: Clinical Biochemistry. - : Elsevier BV. - 1873-2933 .- 0009-9120. ; 38:1, s. 1-8
  • Forskningsöversikt (refereegranskat)abstract
    • Objective: To summarize recent knowledge on the small molecular weight protein cystatin C (cys-C) and its use as a marker of the glomerular filtration rate (GFR). Methods: A multinational expert meeting was held in April 2002 in Marburg, Germany. Contributors summarized their main findings. Conclusions: Cys-C is at least equal if not superior to serum creatinine as a marker of GFR. The independence from height, gender, age. and muscle mass is advantageous. Select patient groups such as children, the elderly, and patients with reduced muscle mass benefit in particular.
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10.
  • Furukawa, Toshi A., et al. (författare)
  • Initial severity of depression and efficacy of cognitive-behavioural therapy: individual-participant data meta-analysis of pill-placebo-controlled trials
  • 2017
  • Ingår i: British Journal of Psychiatry. - : ROYAL COLLEGE OF PSYCHIATRISTS. - 0007-1250 .- 1472-1465. ; 210:3, s. 190-196
  • Forskningsöversikt (refereegranskat)abstract
    • Background The influence of baseline severity has been examined for antidepressant medications but has not been studied properly for cognitive behavioural therapy (CBT) in comparison with pill placebo. Aims To synthesise evidence regarding the influence of initial severity on efficacy of CBT from all randomised controlled trials (RCTs) in which CBT, in face-to-face individual or group format, was compared with pill-placebo control in adults with major depression. Method A systematic review and an individual-participant data meta-analysis using mixed models that included trial effects as random effects. We used multiple imputation to handle missing data. Results We identified five RCTs, and we were given access to individual-level data (n=509) for all five. The analyses revealed that the difference in changes in Hamilton Rating Scale for Depression between CBT and pill placebo was not influenced by baseline severity (interaction P=0.43). Removing the non-significant interaction term from the model, the difference between CBT and pill placebo was a standardised mean difference of 0.22 (95% CI 0.42 to 0.02, P=0.03, l(2)=0%). Conclusions Patients suffering from major depression can expect as much benefit from CBT across the wide range of baseline severity. This finding can help inform individualised treatment decisions by patients and their clinicians.
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