Broaching is a unique machining process with high accuracy and surface quality, which is employed in mass and batch production for the manufacture of components with highly complex geometries. It ...involves the use of multiple-edged complex tools in which the cutting edges are arranged with an offset also known as “rise per tooth” that determines the depth of cut per tooth. This paper presents the state-of-the-art of both the experimental and modelling aspects of broaching, and identifies the most important features related to this machining process. This includes a critical assessment of specifically designed broaching setups and their applicability and/or limitations compared to the machines used in industry. Contributions from academia and industry are included to support a comprehensive report of recent advances, as well as a roadmap for future developments.
Over the last 20 years, multiple interventions to better integrate palliative care and intensive care unit (ICU) care have been evaluated. This systematic review summarizes these studies and their ...outcomes.
We searched MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Cochrane Library, and the Web of Science; performed a search of articles published by opinion leaders in the field; and reviewed hand-search articles as of August 13, 2012. The terms "palliative care" and "intensive care unit" were mapped to MeSH subject headings and "exploded." We included trials of adult patients that evaluated an ICU intervention and addressed Robert Wood Johnson group-identified domains of high-quality end-of-life care in the ICU. We excluded case series, editorials, and review articles. We compared two types of interventions, integrative and consultative, focusing on the outcomes of patient and family satisfaction, mortality, and ICU and hospital length of stay (LOS), because these were most prevalent among studies.
Our search strategy yielded 3328 references, of which we included 37 publications detailing 30 unique interventions. Interventions and outcome measures were heterogeneous, and many studies were underpowered and/or subject to multiple biases. Most of the interventions resulted in a decrease in hospital and ICU LOS. Few interventions significantly affected satisfaction. With one exception, the interventions decreased or had no effect on mortality. There was no evidence of harm from any intervention.
Heterogeneity of interventions made comparison of ICU-based palliative care interventions difficult. However, existing evidence suggests proactive palliative care in the ICU, using either consultative or integrative palliative care interventions, decrease hospital and ICU LOS, do not affect satisfaction, and either decrease or do not affect mortality.
Antiplatelets and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk.
We performed a 3 × 2 partial ...factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation.
There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88; 95% confidence interval CI, 0.67–1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52; 95% confidence interval, 0.28–0.94; P = .03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45; 95% confidence interval, 0.27–0.74), although the number needed to treat still was high (n = 982; 95% confidence interval, 609–2528).
In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials.gov ID: NCT01776424.
To develop evidence-based recommendations for clinicians caring for adults with acute or acute on chronic liver failure in the ICU.
The guideline panel comprised 29 members with expertise in aspects ...of care of the critically ill patient with liver failure and/or methodology. The Society of Critical Care Medicine standard operating procedures manual and conflict-of-interest policy were followed throughout. Teleconferences and electronic-based discussion among the panel, as well as within subgroups, served as an integral part of the guideline development.
The panel was divided into nine subgroups: cardiovascular, hematology, pulmonary, renal, endocrine and nutrition, gastrointestinal, infection, perioperative, and neurology.
We developed and selected population, intervention, comparison, and outcomes questions according to importance to patients and practicing clinicians. For each population, intervention, comparison, and outcomes question, we conducted a systematic review aiming to identify the best available evidence, statistically summarized the evidence whenever applicable, and assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence to decision framework to facilitate recommendations formulation as strong or conditional. We followed strict criteria to formulate best practice statements.
In this article, we report 29 recommendations (from 30 population, intervention, comparison, and outcomes questions) on the management acute or acute on chronic liver failure in the ICU, related to five groups (cardiovascular, hematology, pulmonary, renal, and endocrine). Overall, six were strong recommendations, 19 were conditional recommendations, four were best-practice statements, and in two instances, the panel did not issue a recommendation due to insufficient evidence.
Multidisciplinary international experts were able to formulate evidence-based recommendations for the management acute or acute on chronic liver failure in the ICU, acknowledging that most recommendations were based on low-quality indirect evidence.
The methane‐to‐methanol (MtM) conversion via the oxygen looping approach using copper‐exchanged zeolites has been extensively studied over the last decade. While a lot of research has focussed on ...maximizing yield and selectivity, little has been directed toward productivity—a metric far more meaningful for evaluating industrial potential. Using copper‐exchanged zeolite omega (Cu‐omega), a material highly active and selective for the MtM conversion using the isothermal oxygen looping approach, we show that this material exhibits unprecedented potential for industrial valorization. In doing so, we also present a novel methodology combining operando XAS and mass spectrometry for the screening of materials for the MtM conversion in oxygen looping mode.
Cu‐omega (MAZ) is a very active and selective material for the methane‐to‐methanol (MtM) conversion using the oxygen looping approach. By determining the productivity via a novel screening method combining operando XAS and mass spectrometry, this body of work shows the potential this material exhibits for industrial valorization, as well as a screening method for other materials utilizing the oxygen looping approach.
During development, activity-dependent synaptic plasticity refines neuronal networks with high precision. For example, spontaneous activity helps sorting synaptic inputs with similar activity ...patterns into clusters to enhance neuronal computations in the mature brain. Here, we show that TrkB activation and postsynaptic brain-derived neurotrophic factor (BDNF) are required for synaptic clustering in developing hippocampal neurons. Moreover, BDNF and TrkB modulate transmission at synapses depending on their clustering state, indicating that endogenous BDNF/TrkB signaling stabilizes locally synchronized synapses. Together with our previous data on proBDNF/p75NTR signaling, these findings suggest a push-pull plasticity mechanism for synaptic clustering: BDNF stabilizes clustered synapses while proBDNF downregulates out-of-sync synapses. This idea is supported by our observation that synaptic clustering requires matrix-metalloproteinase-9 activity, a proBDNF-to-BDNF converting enzyme. Finally, NMDA receptor activation mediates out-of-sync depression upstream of proBDNF signaling. Together, these data delineate an efficient plasticity mechanism where proBDNF and mature BDNF establish synaptic clustering through antagonistic modulation of synaptic transmission.
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•BDNF/TrkB signaling is required for functional synaptic clustering in hippocampus•Exogenous BDNF activates “out of sync”; blocking TrkB eliminates “in-sync” synapses•Clustering requires activity of MMP9, a proBDNF-to-BDNF conversion enzyme•NMDAR activity downregulates locally desynchronized synapses upstream of proBDNF
Niculescu et al. found that synaptic clustering requires BDNF/TrkB signaling, activity of the proBDNF-to-BDNF conversion enzyme MMP9, and NMDA receptor activation. Their study delineates a push-pull plasticity mechanism where BDNF stabilizes clustered synapses while its precursor, proBDNF, depresses unclustered synapses, together ensuring robust clustering of synaptic inputs in developing neurons.
The globalization of clinical trials has highlighted geographic variations in patient characteristics, event rates, and treatment effects. We investigated these further in PARADIGM-HF, the largest ...and most globally representative trial in heart failure (HF) to date.
We looked at five regions: North America (NA) 602 (8%), Western Europe (WE) 1680 (20%), Central/Eastern Europe/Russia (CEER) 2762 (33%), Latin America (LA) 1433 (17%), and Asia-Pacific (AP) 1487 (18%). Notable differences included: WE patients (mean age 68 years) and NA (65 years) were older than AP (58 years) and LA (63 years) and had more coronary disease; NA and CEER patients had the worst signs, symptoms, and functional status. North American patients were the most likely to have a defibrillating-device (54 vs. 2% AP) and least likely prescribed a mineralocorticoid receptor antagonist (36 vs. 65% LA). Other evidence-based therapies were used most frequently in NA and WE. Rates of the primary composite outcome of cardiovascular (CV) death or HF hospitalization (per 100 patient-years) varied among regions: NA 13.6 (95% CI 11.7-15.7) WE 9.6 (8.6-10.6), CEER 12.3 (11.4-13.2), LA 11.2 (10.0-12.5), and AP 12.5 (11.3-13.8). After adjustment for prognostic variables, relative to NA, the risk of CV death was higher in LA and AP and the risk of HF hospitalization lower in WE. The benefit of sacubitril/valsartan was consistent across regions.
There were many regional differences in PARADIGM-HF, including in age, symptoms, comorbidity, background therapy, and event-rates, although these did not modify the benefit of sacubitril/valsartan. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255.
In the absence of active tuberculosis, a positive tuberculin skin test (TST) or interferon-γ release assay (IGRA) result defines latent infection with Mycobacterium tuberculosis, although test ...results may vary depending on immunodeficiency.
This study compared the performance of TST and IGRAs in five different groups of immunocompromised patients, and evaluated their ability to identify those at risk for development of tuberculosis.
Immunocompromised patients with HIV infection, chronic renal failure, rheumatoid arthritis, solid-organ or stem-cell transplantation, and healthy control subjects were evaluated head-to-head by the TST, QuantiFERON-TB-Gold in-tube test (ELISA), and T-SPOT.TB test (enzyme-linked immunospot) at 17 centers in 11 European countries. Development of tuberculosis was assessed during follow-up.
Frequencies of positive test results varied from 8.7 to 15.9% in HIV infection (n = 768), 25.3 to 30.6% in chronic renal failure (n = 270), 25.0% to 37.2% in rheumatoid arthritis (n = 199), 9.0 to 20.0% in solid-organ transplant recipients (n = 197), 0% to 5.8% in stem-cell transplant recipients (n = 103), and 11.2 to 15.2% in immunocompetent control subjects (n = 211). Eleven patients (10 with HIV infection and one solid-organ transplant recipient) developed tuberculosis during a median follow-up of 1.8 (interquartile range, 0.2-3.0) years. Six of the 11 patients had a negative or indeterminate test result in all three tests at the time of screening. Tuberculosis incidence was generally low, but higher in HIV-infected individuals with a positive TST (3.25 cases per 100 person-years) than with a positive ELISA (1.31 cases per 100 person-years) or enzyme-linked immunospot result (1.78 cases per 100 person-years). No cases of tuberculosis occurred in patients who received preventive chemotherapy.
Among immunocompromised patients evaluated in this study, progression toward tuberculosis was highest in HIV-infected individuals and was poorly predicted by TST or IGRAs. Clinical trial registered with www.clinicaltrials.gov (NCT 00707317).
Olanzapine and quetiapine are routinely used off-label at lower doses, though it remains unclear whether treatment is associated with mortality. Here, we examined the associations between low-dose ...olanzapine/quetiapine, defined as 5 mg/day of olanzapine equivalents (OE) with cardiometabolic mortality in a population-based, longitudinal cohort of individuals who sought specialized psychiatric services. Through cross-linked Swedish registries, 428,525 individuals without psychotic, bipolar, or cardiometabolic disorders, or previous treatment with antipsychotics or cardiometabolic-related drugs were followed for up to 10.5 years. Extended stratified Cox proportional hazards regressions were employed to estimate the hazard ratios (HR) of cardiometabolic mortality as a function of cumulative OE exposures, adjusted for age, sex, inpatient care, and time-dependent psychiatric diagnoses and treatments. Individuals were followed for a total of 2.1 million person-years. Treatment with olanzapine/quetiapine occurred in 18,317 of the cohort. In total, 2606 cardiometabolic-related deaths occurred. Treatment status (treated vs. untreated) was not significantly associated with cardiometabolic mortality (adjusted HR 0.86, 95% CI 0.64–1.15, P = 0.307). However, compared to no treatment, treatment for <6 months was significantly associated with a reduced risk (adjusted HR 0.56, 95% CI 0.37–0.87, P = 0.010) whereas treatment for 6–12 months was significantly associated with an increased risk (adjusted HR 1.89, 95% CI 1.22–2.92, P = 0.004), but not significantly beyond 12 months. Among those treated, each year exposed to an average 5 mg/day was significantly associated with increased cardiometabolic mortality (adjusted HR 1.45, 95% CI 1.06–1.99, P = 0.019). Overall, low-dose olanzapine/quetiapine treatment was weakly associated with cardiometabolic mortality. Clinicians should consider potential cardiometabolic sequelae at lower doses.
•Off-label, low-dose olanzapine/quetiapine treatment was weakly associated with cardiometabolic mortality.•Treatment status (treated vs untreated) was not significantly associated with cardiometabolic mortality.•Treatment for 6–12 months was significantly associated with an increased risk compared to no treatment.•Among those treated, each year exposed was significantly associated with an increased risk.•Clinicians should consider cardiometabolic consequences regardless of prescribed dose or length of treatment.
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