Summary
Objective
Women with pre‐eclampsia have elevated circulating levels of soluble fms‐like tyrosine kinase‐1 (sFlt‐1). Statins can reduce sFlt‐1 from cultured cells and improve pregnancy outcome ...in animals with a pre‐eclampsia‐like syndrome. We investigated the effect of pravastatin on plasma sFlt‐1 levels during pre‐eclampsia.
Design
Blinded (clinician and participant), proof of principle, placebo‐controlled trial.
Setting
Fifteen UK maternity units.
Population
We used a minimisation algorithm to assign 62 women with early‐onset pre‐eclampsia (24+0–31+6 weeks of gestation) to receive pravastatin 40 mg daily (n = 30) or matched placebo (n = 32), from randomisation to childbirth.
Primary outcome
Difference in mean plasma sFlt‐1 levels over the first 3 days following randomisation.
Results
The difference in the mean maternal plasma sFlt‐1 levels over the first 3 days after randomisation between the pravastatin (n = 27) and placebo (n = 29) groups was 292 pg/ml (95% CI −1175 to 592; P = 0.5), and over days 1–14 was 48 pg/ml (95% CI −1009 to 913; P = 0.9). Women who received pravastatin had a similar length of pregnancy following randomisation compared with those who received placebo (hazard ratio 0.84; 95% CI 0.50–1.40; P = 0.6). The median time from randomisation to childbirth was 9 days (interquartile range IQR 5–14 days) for the pravastatin group and 7 days (IQR 4–11 days) for the placebo group. There were three perinatal deaths in the placebo‐treated group and no deaths or serious adverse events attributable to pravastatin.
Conclusions
We found no evidence that pravastatin lowered maternal plasma sFlt‐1 levels once early‐onset pre‐eclampsia had developed. Pravastatin appears to have no adverse perinatal effects.
Tweetable
Pravastatin does not improve maternal plasma sFlt‐1 or placental growth factor levels following a diagnosis of early preterm pre‐eclampsia #clinicaltrial finds.
Tweetable
Pravastatin does not improve maternal plasma sFlt‐1 or placental growth factor levels following a diagnosis of early preterm pre‐eclampsia #clinicaltrial finds.
Thanks to ready access to hydrogen breath testing, small intestinal bacterial overgrowth (SIBO) is now commonly diagnosed among individuals presenting with a variety of gastrointestinal and even ...nongastrointestinal symptoms and is increasingly implicated in lay press and media in the causation of a diverse array of disorders. Its definition, however, remains controversial and true prevalence, accordingly, undefined. The purpose of this review, therefore, was to provide a historical background to the concept of SIBO, critically review current concepts of SIBO (including symptomatology, pathophysiology, clinical consequences, diagnosis and treatment), define unanswered questions and provide a road map toward their resolution.
Best Practice Advice statements were developed following discussion by the 3 authors. Two authors each developed text around certain Best Practice Advice based on a review of available literature. All 3 authors reviewed the complete draft and after discussion, redrafting, and further review and revision, all of the authors agreed on a final draft.
The definition of SIBO as a clinical entity lacks precision and consistency; it is a term generally applied to a clinical disorder where symptoms, clinical signs, and/or laboratory abnormalities are attributed to changes in the numbers of bacteria or in the composition of the bacterial population in the small intestine.
Symptoms traditionally linked to SIBO include bloating, diarrhea, and abdominal pain/discomfort. Steatorrhea may be seen in more severe cases.
There is insufficient evidence to support the use of inflammatory markers, such as fecal calprotectin to detect SIBO.
Laboratory findings can include elevated folate and, less commonly, vitamin B-12 deficiency, or other nutritional deficiencies.
A major impediment to our ability to accurately define SIBO is our limited understanding of normal small intestinal microbial populations—progress in sampling technology and techniques to enumerate bacterial populations and their metabolic products should provide much needed clarity.
Controversy remains concerning the role of SIBO in the pathogenesis of common functional symptoms, such as those regarded as components of irritable bowel syndrome.
Management should focus on the identification and correction (where possible) of underlying causes, correction of nutritional deficiencies, and the administration of antibiotics. This is especially important for patients with significant maldigestion and malabsorption.
Although irritable bowel syndrome has been shown to respond to therapy with a poorly absorbed antibiotic, the role of SIBO or its eradication in the genesis of this response warrants further confirmation in randomized controlled trials.
There is a limited database to guide the clinician in developing antibiotic strategies for SIBO, in any context. Therapy remains, for the most part, empiric but must be ever mindful of the potential risks of long-term broad-spectrum antibiotic therapy.
Human intestinal microbiota create a complex polymi-crobial ecology. This is characterised by its high population density, wide diversity and complexity of interaction. Any dysbalance of this complex ...intestinal microbiome, both qualitative and quantitative, might have serious health consequence for a macro-organism, including small intestinal bacterial overgrowth syndrome (SIBO).SIBO is defined as an increase in the number and/or alteration in the type of bacteria in the upper gastro-intestinal tract. There...
Solar‐blind deep ultraviolet (DUV) photodetectors have been a hot topic in recent years because of their wide commercial and military applications. A wide bandgap (4.68 eV) of ternary oxide Zn2GeO4 ...makes it an ideal material for the solar‐blind DUV detection. Unfortunately, the sensing performance of previously reported photodetectors based on Zn2GeO4 nanowires has been unsatisfactory for practical applications, because they suffer from long response and decay times, low responsivity, and quantum efficiency. Here, high‐performance solar‐blind DUV photodetectors are developed based on individual single‐crystalline Zn2GeO4 nanowires. The transport mechanism is discussed in the frame of the small polaron theory. In situ electrical characterization of individual Zn2GeO4 nanowires reveals a high gain under high energy electron beam. The devices demonstrate outstanding solar‐blind light sensing performances: a responsivity of 5.11 × 103 A W−1, external quantum efficiency of 2.45 × 106%, detectivity of ≈2.91 × 1011 Jones, τrise ≈ 10 ms, and τdecay ≈ 13 ms, which are superior to all reported Zn2GeO4 and other ternary oxide nanowire photodetectors. These results render the Zn2GeO4 nanowires particularly valuable for optoelectronic devices.
High quality single‐crystalline Zn2GeO4 nanowires are synthesized via chemical vapor deposition. Photodetectors based on individual nanowires demonstrate outstanding solar‐blind light sensing performance: a responsivity of 5.11 × 103 A W−1, external quantum efficiency of 2.45 × 106%, detectivity of ≈ 2.91 × 1011 Jones, τrise ≈ 10 ms, and τdecay ≈ 13 ms.
We conducted a systematic review and meta-analysis to compare the prevalence of small intestinal bacterial overgrowth (SIBO) in patients with irritable bowel syndrome (IBS) and controls.
Electronic ...databases were searched up to December 2018 for studies reporting SIBO prevalence in patients with IBS. Prevalence rates, odds ratios (ORs), and 95% confidence intervals (CIs) of SIBO in patients with IBS and controls were calculated.
We included 25 studies with 3,192 patients with IBS and 3,320 controls. SIBO prevalence in patients with IBS was significantly increased compared with controls (OR = 3.7, 95% CI 2.3-6.0). In studies using only healthy controls, the OR for SIBO in patients with IBS was 4.9 (95% CI 2.8-8.6). With breath testing, SIBO prevalence in patients with IBS was 35.5% (95% CI 33.6-37.4) vs 29.7% (95% CI 27.6-31.8) in controls. Culture-based studies yielded a SIBO prevalence of 13.9% (95% CI 11.5-16.4) in patients with IBS and 5.0% (95% CI 3.9-6.2) in controls with a cutoff value of 10 colony-forming units per milliliter vs 33.5% (95% CI 30.1-36.9) in patients with IBS and 8.2% (95% CI 6.8-9.6) in controls with a cutoff value of 10 colony-forming unit per milliliter, respectively. SIBO prevalence diagnosed by lactulose breath test is much greater in both patients with IBS (3.6-fold) and controls (7.6-fold) compared with glucose breath test. Similar difference is seen when lactulose breath test is compared with culture methods. OR for SIBO in patients with IBS-diarrhea compared with IBS-constipation was 1.86 (95% CI 1.83-2.8). Methane-positive breath tests were significantly more prevalent in IBS-constipation compared with IBS-diarrhea (OR = 2.3, 95% CI 1.2-4.2). In patients with IBS, proton pump inhibitor was not associated with SIBO (OR = 0.8, 95% CI 0.5-1.5, P = 0.55).
This systematic review and meta-analysis suggests a link between IBS and SIBO. However, the overall quality of the evidence is low. This is mainly due to substantial "clinical heterogeneity" due to lack of uniform selection criteria for cases and controls and limited sensitivity and specificity of the available diagnostic tests.
Depression is the leading cause of disability worldwide, and half of patients with depression have treatment-resistant depression. Intermittent theta-burst stimulation (iTBS) is approved by the U.S. ...Food and Drug Administration for the treatment of treatment-resistant depression but is limited by suboptimal efficacy and a 6-week duration. The authors addressed these limitations by developing a neuroscience-informed accelerated iTBS protocol, Stanford neuromodulation therapy (SNT; previously referred to as Stanford accelerated intelligent neuromodulation therapy, or SAINT). This protocol was associated with a remission rate of ∼90% after 5 days of open-label treatment. Here, the authors report the results of a sham-controlled double-blind trial of SNT for treatment-resistant depression.
Participants with treatment-resistant depression currently experiencing moderate to severe depressive episodes were randomly assigned to receive active or sham SNT. Resting-state functional MRI was used to individually target the region of the left dorsolateral prefrontal cortex most functionally anticorrelated with the subgenual anterior cingulate cortex. The primary outcome was score on the Montgomery-Åsberg Depression Rating Scale (MADRS) 4 weeks after treatment.
At the planned interim analysis, 32 participants with treatment-resistant depression had been enrolled, and 29 participants who continued to meet inclusion criteria received either active (N=14) or sham (N=15) SNT. The mean percent reduction from baseline in MADRS score 4 weeks after treatment was 52.5% in the active treatment group and 11.1% in the sham treatment group.
SNT, a high-dose iTBS protocol with functional-connectivity-guided targeting, was more effective than sham stimulation for treatment-resistant depression. Further trials are needed to determine SNT's durability and to compare it with other treatments.
Small intestinal bacterial overgrowth (SIBO), characterized by the presence of excessive bacteria in the small intestine, is typically described as a malabsorptive syndrome occurring in the context ...of gut stasis syndromes. SIBO is now considered to be a disorder associated with diverse clinical conditions without classic risk factors for SIBO and a cause of several nonspecific gastrointestinal and nongastrointestinal symptoms. Because there is currently no gold standard for diagnosing SIBO, its prevalence and role in the pathogenesis of other diseases remain uncertain; as does optimal treatment of patients with relapsing symptoms.
Understanding Blind Deconvolution Algorithms Levin, A.; Weiss, Y.; Durand, F. ...
IEEE transactions on pattern analysis and machine intelligence,
12/2011, Volume:
33, Issue:
12
Journal Article
Peer reviewed
Blind deconvolution is the recovery of a sharp version of a blurred image when the blur kernel is unknown. Recent algorithms have afforded dramatic progress, yet many aspects of the problem remain ...challenging and hard to understand. The goal of this paper is to analyze and evaluate recent blind deconvolution algorithms both theoretically and experimentally. We explain the previously reported failure of the naive MAP approach by demonstrating that it mostly favors no-blur explanations. We show that, using reasonable image priors, a naive simulations MAP estimation of both latent image and blur kernel is guaranteed to fail even with infinitely large images sampled from the prior. On the other hand, we show that since the kernel size is often smaller than the image size, a MAP estimation of the kernel alone is well constrained and is guaranteed to succeed to recover the true blur. The plethora of recent deconvolution techniques makes an experimental evaluation on ground-truth data important. As a first step toward this experimental evaluation, we have collected blur data with ground truth and compared recent algorithms under equal settings. Additionally, our data demonstrate that the shift-invariant blur assumption made by most algorithms is often violated.
Peer review may be “single-blind,” in which reviewers are aware of the names and affiliations of paper authors, or “double-blind,” in which this information is hidden. Noting that computer science ...research often appears first or exclusively in peer-reviewed conferences rather than journals, we study these two reviewing models in the context of the 10th Association for Computing Machinery International Conference on Web Search and Data Mining, a highly selective venue (15.6% acceptance rate) in which expert committee members review full-length submissions for acceptance. We present a controlled experiment in which four committee members review each paper. Two of these four reviewers are drawn from a pool of committee members with access to author information; the other two are drawn from a disjoint pool without such access. This information asymmetry persists through the process of bidding for papers, reviewing papers, and entering scores. Reviewers in the single-blind condition typically bid for 22% fewer papers and preferentially bid for papers from top universities and companies. Once papers are allocated to reviewers, single-blind reviewers are significantly more likely than their double-blind counterparts to recommend for acceptance papers from famous authors, top universities, and top companies. The estimated odds multipliers are tangible, at 1.63, 1.58, and 2.10, respectively.
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