EARLYDRAIN- outcome after early lumbar CSF-drainage in aneurysmal subarachnoid hemorrhage: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Aneurysmal subarachnoid hemorrhage (SAH) may be complicated by delayed cerebral ischemia, which is a major cause of unfavorable clinical outcome and death in SAH-patients. Delayed cerebral ischemia is presumably related to the development of vasospasm triggered by the presence of blood in the basal cisterns. To date, oral application of the calcium antagonist nimodipine is the only prophylactic treatment for vasospasm recognized under international guidelines.</p> <p>In retrospective trials lumbar drainage of cerebrospinal fluid has been shown to be a safe and feasible measure to remove the blood from the basal cisterns and decrease the incidence of delayed cerebral ischemia and vasospasm in the respective study populations. However, the efficacy of lumbar drainage has not been evaluated prospectively in a randomized controlled trial yet.</p> <p>Methods/Design</p> <p>This is a protocol for a 2-arm randomized controlled trial to compare an intervention group receiving early continuous lumbar CSF-drainage and standard neurointensive care to a control group receiving standard neurointensive care only. Adults suffering from a first aneurysmal subarachnoid hemorrhage whose aneurysm has been secured by means of coiling or clipping are eligible for trial participation. The effect of early CSF drainage (starting < 72 h after securing the aneurysm) will be measured in the following ways: the primary endpoint will be disability after 6 months, assessed by a blinded investigator during a personal visit or standardized telephone interview using the modified Rankin Scale. Secondary endpoints include mortality after 6 months, angiographic vasospasm, transcranial Doppler sonography (TCD) mean flow velocity in both middle cerebral arteries and rate of shunt insertion at 6 months after hospital discharge.</p> <p>Discussion</p> <p>Here, we present the study design of a multicenter prospective randomized controlled trial to investigate whether early application of a lumbar drainage improves clinical outcome after aneurysmal subarachnoid hemorrhage.</p> <p>Trial registration</p> <p>www.clinicaltrials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01258257">NCT01258257</a></p

Quantifying Selective Reporting and the Proteus Phenomenon for Multiple Datasets with Similar Bias

Meta-analyses play an important role in synthesizing evidence from diverse studies and datasets that address similar questions. A major obstacle for meta-analyses arises from biases in reporting. In particular, it is speculated that findings which do not achieve formal statistical significance are less likely reported than statistically significant findings. Moreover, the patterns of bias can be complex and may also depend on the timing of the research results and their relationship with previously published work. In this paper, we present an approach that is specifically designed to analyze large-scale datasets on published results. Such datasets are currently emerging in diverse research fields, particularly in molecular medicine. We use our approach to investigate a dataset on Alzheimer's disease (AD) that covers 1167 results from case-control studies on 102 genetic markers. We observe that initial studies on a genetic marker tend to be substantially more biased than subsequent replications. The chances for initial, statistically non-significant results to be published are estimated to be about 44% (95% CI, 32% to 63%) relative to statistically significant results, while statistically non-significant replications have almost the same chance to be published as statistically significant replications (84%; 95% CI, 66% to 107%). Early replications tend to be biased against initial findings, an observation previously termed Proteus phenomenon: The chances for non-significant studies going in the same direction as the initial result are estimated to be lower than the chances for non-significant studies opposing the initial result (73%; 95% CI, 55% to 96%). Such dynamic patters in bias are difficult to capture by conventional methods, where typically simple publication bias is assumed to operate. Our approach captures and corrects for complex dynamic patterns of bias, and thereby helps generating conclusions from published results that are more robust against the presence of different coexisting types of selective reporting

Silkworm expression system as a platform technology in life science

Many recombinant proteins have been successfully produced in silkworm larvae or pupae and used for academic and industrial purposes. Several recombinant proteins produced by silkworms have already been commercialized. However, construction of a recombinant baculovirus containing a gene of interest requires tedious and troublesome steps and takes a long time (3–6 months). The recent development of a bacmid, Escherichia coli and Bombyx mori shuttle vector, has eliminated the conventional tedious procedures required to identify and isolate recombinant viruses. Several technical improvements, including a cysteine protease or chitinase deletion bacmid and chaperone-assisted expression and coexpression, have led to significantly increased protein yields and reduced costs for large-scale production. Terminal N-acetyl glucosamine and galactose residues were found in the N-glycan structures produced by silkworms, which are different from those generated by insect cells. Genomic elucidation of silkworm has opened a new chapter in utilization of silkworm. Transgenic silkworm technology provides a stable production of recombinant protein. Baculovirus surface display expression is one of the low-cost approaches toward silkworm larvae-derived recombinant subunit vaccines. The expression of pharmaceutically relevant proteins, including cell/viral surface proteins, membrane proteins, and guanine nucleotide-binding protein (G protein) coupled receptors, using silkworm larvae or cocoons has become very attractive. Silkworm biotechnology is an innovative and easy approach to achieve high protein expression levels and is a very promising platform technology in the field of life science. Like the “Silkroad,” we expect that the “Bioroad” from Asia to Europe will be established by the silkworm expression system

Apoptosis of CD4+CD25high T Cells in Type 1 Diabetes May Be Partially Mediated by IL-2 Deprivation

from T1D subjects. in T1D may be caught up in a relatively deficient cytokine milieu. function in subjects predisposed to T1D

The role of peptides in bone healing and regeneration: A systematic review

Background: Bone tissue engineering and the research surrounding peptides has expanded significantly over the last few decades. Several peptides have been shown to support and stimulate the bone healing response and have been proposed as therapeutic vehicles for clinical use. The aim of this comprehensive review is to present the clinical and experimental studies analysing the potential role of peptides for bone healing and bone regeneration. Methods: A systematic review according to PRISMA guidelines was conducted. Articles presenting peptides capable of exerting an upregulatory effect on osteoprogenitor cells and bone healing were included in the study. Results: Based on the available literature, a significant amount of experimental in vitro and in vivo evidence exists. Several peptides were found to upregulate the bone healing response in experimental models and could act as potential candidates for future clinical applications. However, from the available peptides that reached the level of clinical trials, the presented results are limited. Conclusion: Further research is desirable to shed more light into the processes governing the osteoprogenitor cellular responses. With further advances in the field of biomimetic materials and scaffolds, new treatment modalities for bone repair will emerge

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Measurements of Higgs bosons decaying to bottom quarks from vector boson fusion production with the ATLAS experiment at √=13TeV

The paper presents a measurement of the Standard Model Higgs Boson decaying to b-quark pairs in the vector boson fusion (VBF) production mode. A sample corresponding to 126 fb−1 of s√=13TeV proton–proton collision data, collected with the ATLAS experiment at the Large Hadron Collider, is analyzed utilizing an adversarial neural network for event classification. The signal strength, defined as the ratio of the measured signal yield to that predicted by the Standard Model for VBF Higgs production, is measured to be 0.95+0.38−0.36 , corresponding to an observed (expected) significance of 2.6 (2.8) standard deviations from the background only hypothesis. The results are additionally combined with an analysis of Higgs bosons decaying to b-quarks, produced via VBF in association with a photon

Muon reconstruction and identification efficiency in ATLAS using the full Run 2 pp collision data set at \sqrt{s}=13 TeV

This article documents the muon reconstruction and identification efficiency obtained by the ATLAS experiment for 139 \hbox {fb}^{-1} of pp collision data at \sqrt{s}=13 TeV collected between 2015 and 2018 during Run 2 of the LHC. The increased instantaneous luminosity delivered by the LHC over this period required a reoptimisation of the criteria for the identification of prompt muons. Improved and newly developed algorithms were deployed to preserve high muon identification efficiency with a low misidentification rate and good momentum resolution. The availability of large samples of Z\rightarrow \mu \mu and J/\psi \rightarrow \mu \mu decays, and the minimisation of systematic uncertainties, allows the efficiencies of criteria for muon identification, primary vertex association, and isolation to be measured with an accuracy at the per-mille level in the bulk of the phase space, and up to the percent level in complex kinematic configurations. Excellent performance is achieved over a range of transverse momenta from 3 GeV to several hundred GeV, and across the full muon detector acceptance of |\eta |<2.7

Measurements of differential cross-sections in top-quark pair events with a high transverse momentum top quark and limits on beyond the Standard Model contributions to top-quark pair production with the ATLAS detector at √s = 13 TeV

Cross-section measurements of top-quark pair production where the hadronically decaying top quark has transverse momentum greater than 355 GeV and the other top quark decays into ℓνb are presented using 139 fb−1 of data collected by the ATLAS experiment during proton-proton collisions at the LHC. The fiducial cross-section at s = 13 TeV is measured to be σ = 1.267 ± 0.005 ± 0.053 pb, where the uncertainties reflect the limited number of data events and the systematic uncertainties, giving a total uncertainty of 4.2%. The cross-section is measured differentially as a function of variables characterising the tt¯ system and additional radiation in the events. The results are compared with various Monte Carlo generators, including comparisons where the generators are reweighted to match a parton-level calculation at next-to-next-to-leading order. The reweighting improves the agreement between data and theory. The measured distribution of the top-quark transverse momentum is used to search for new physics in the context of the effective field theory framework. No significant deviation from the Standard Model is observed and limits are set on the Wilson coefficients of the dimension-six operators OtG and Otq(8), where the limits on the latter are the most stringent to date. [Figure not available: see fulltext.]