Minotaur: A SIMD-Oriented Synthesizing Superoptimizer

Minotaur is a superoptimizer for LLVM's intermediate representation that focuses on integer SIMD instructions, both portable and specific to x86-64. We created it to attack problems in finding missing peephole optimizations for SIMD instructions-this is challenging because there are many such instructions and they can be semantically complex. Minotaur runs a hybrid synthesis algorithm where instructions are enumerated concretely, but literal constants are generated by the solver. We use Alive2 as a verification engine; to do this we modified it to support synthesis and also to support a large subset of Intel's vector instruction sets (SSE, AVX, AVX2, and AVX-512). Minotaur finds many profitable optimizations that are missing from LLVM. It achieves limited speedups on the integer parts of SPEC CPU2017, around 1.3%, and it speeds up the test suite for the libYUV library by 2.2%, on average, and by 1.64x maximum, when targeting an Intel Cascade Lake processor

Facile synthesis of Al-stabilized lithium garnets by a solution-combustion technique for all solid-state batteries

Garnet-type solid electrolytes with cubic modification (c-LLZO, Li7La3Zr2O12) are considered to be one of the most promising candidates for SSLBs with desirable properties such as high ionic conductivity (about 1 mS cm−1) at room temperature, a wide electrochemical operational window, and good stability against reduction by Li metal. The synthesis and processing of garnets through conventional wet-chemical, solid-state reaction and nitrate-combustion approaches often requires one or more of the following processing conditions (energy intensive milling steps, multiple and long periods of calcination) to attain a conductive cubic phase making synthesis time intensive. Herein, we report a facile fuel-assisted solution combustion method using carbohydrazide–nitrate mixtures to synthesize cubic-Li6.28Al0.24La3Zr2O12 (Al-LLZO); compared to other nitrate-combustion approaches, utilizing a nitrogen containing fuel source (CH6N4O) offers drastic reduction in the synthesis duration at relatively low temperatures. Selection of the right fuel to oxidizer ratio and annealing conditions is found to be critical for attaining phase purity and particle growth size of LLZO powders. Cubic phase Al-LLZO with a particle size of up to ∼200 nm was attained at temperatures as low as 800 °C upon calcining the as-combusted powders for 4 h. The green pellets attained high relative densities of 90–92% and ionic conductivities up to 0.45 mS cm−1 at low sintering conditions of 1100 °C for 6 h compared to longer sintering duration (∼10–24 h) for LLZO prepared with a common solid-state reaction or wet chemical methods using conventional pressure-less sintering methods. Sintered pellets exhibited a low activation energy of 0.29 eV likely due to the low grain boundary resistance. Synthesizing sub-micron sized Al-LLZO powders through low-cost facile synthesis approaches is of great importance in the fabrication of composite electrolytes and catholytes

Does a mobile phone depression-screening app motivate mobile phone users with high depressive symptoms to seek a health care professional's help?

Background: The objective of disease screening is to encourage high-risk subjects to seek health care diagnosis and treatment. Mobile phone apps can effectively screen mental health conditions, including depression. However, it is not known how effective such screening methods are in motivating users to discuss the obtained results of such apps with health care professionals. Does a mobile phone depression-screening app motivate users with high depressive symptoms to seek health care professional advice? This study aimed to address this question. Method: This was a single-cohort, prospective, observational study of a free mobile phone depression app developed in English and released on Apple's App Store. Apple App Store users (aged 18 or above) in 5 countries, that is, Australia, Canada, New Zealand (NZ), the United Kingdom (UK), and the United States (US), were recruited directly via the app's download page. The participants then completed the Patient Health Questionnaire (PHQ-9), and their depression screening score was displayed to them. If their score was 11 or above and they had never been diagnosed with depression before, they were advised to take their results to their health care professional. They were to follow up after 1 month. Results: A group of 2538 participants from the 5 countries completed PHQ-9 depression screening with the app. Of them, 322 participants were found to have high depressive symptoms and had never been diagnosed with depression, and received advice to discuss their results with health care professionals. About 74% of those completed the follow-up; approximately 38% of these self-reported consulting their health care professionals about their depression score. Only positive attitude toward depression as a real disease was associated with increased follow-up response rate (odds ratio (OR) 3.2, CI 1.38-8.29). Conclusions: A mobile phone depression-screening app motivated some users to seek a depression diagnosis. However, further study should investigate how other app users use the screening results provided by such apps.10 page(s

Odanacatib for the treatment of postmenopausal osteoporosis : Results of the LOFT multicentre, randomised, double-blind, placebo-controlled trial and LOFT Extension study

Background Odanacatib, a cathepsin K inhibitor, reduces bone resorption while maintaining bone formation. Previous work has shown that odanacatib increases bone mineral density in postmenopausal women with low bone mass. We aimed to investigate the efficacy and safety of odanacatib to reduce fracture risk in postmenopausal women with osteoporosis. Methods The Long-term Odanacatib Fracture Trial (LOFT) was a multicentre, randomised, double-blind, placebo-controlled, event-driven study at 388 outpatient clinics in 40 countries. Eligible participants were women aged at least 65 years who were postmenopausal for 5 years or more, with a femoral neck or total hip bone mineral density T-score between −2·5 and −4·0 if no previous radiographic vertebral fracture, or between −1·5 and −4·0 with a previous vertebral fracture. Women with a previous hip fracture, more than one vertebral fracture, or a T-score of less than −4·0 at the total hip or femoral neck were not eligible unless they were unable or unwilling to use approved osteoporosis treatment. Participants were randomly assigned (1:1) to either oral odanacatib (50 mg once per week) or matching placebo. Randomisation was done using an interactive voice recognition system after stratification for previous radiographic vertebral fracture, and treatment was masked to study participants, investigators and their staff, and sponsor personnel. If the study completed before 5 years of double-blind treatment, consenting participants could enrol in a double-blind extension study (LOFT Extension), continuing their original treatment assignment for up to 5 years from randomisation. Primary endpoints were incidence of vertebral fractures as assessed using radiographs collected at baseline, 6 and 12 months, yearly, and at final study visit in participants for whom evaluable radiograph images were available at baseline and at least one other timepoint, and hip and non-vertebral fractures adjudicated as being a result of osteoporosis as assessed by clinical history and radiograph. Safety was assessed in participants who received at least one dose of study drug. The adjudicated cardiovascular safety endpoints were a composite of cardiovascular death, myocardial infarction, or stroke, and new-onset atrial fibrillation or flutter. Individual cardiovascular endpoints and death were also assessed. LOFT and LOFT Extension are registered with ClinicalTrials.gov (number NCT00529373) and the European Clinical Trials Database (EudraCT number 2007-002693-66). Findings Between Sept 14, 2007, and Nov 17, 2009, we randomly assigned 16 071 evaluable patients to treatment: 8043 to odanacatib and 8028 to placebo. After a median follow-up of 36·5 months (IQR 34·43–40·15) 4297 women assigned to odanacatib and 3960 assigned to placebo enrolled in LOFT Extension (total median follow-up 47·6 months, IQR 35·45–60·06). In LOFT, cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 3·7% (251/6770) versus 7·8% (542/6910), hazard ratio (HR) 0·46, 95% CI 0·40–0·53; hip fractures 0·8% (65/8043) versus 1·6% (125/8028), 0·53, 0·39–0·71; non-vertebral fractures 5·1% (412/8043) versus 6·7% (541/8028), 0·77, 0·68–0·87; all p<0·0001. Combined results from LOFT plus LOFT Extension for cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 4·9% (341/6909) versus 9·6% (675/7011), HR 0·48, 95% CI 0·42–0·55; hip fractures 1·1% (86/8043) versus 2·0% (162/8028), 0·52, 0·40–0·67; non-vertebral fractures 6·4% (512/8043) versus 8·4% (675/8028), 0·74, 0·66–0·83; all p<0·0001. In LOFT, the composite cardiovascular endpoint of cardiovascular death, myocardial infarction, or stroke occurred in 273 (3·4%) of 8043 patients in the odanacatib group versus 245 (3·1%) of 8028 in the placebo group (HR 1·12, 95% CI 0·95–1·34; p=0·18). New-onset atrial fibrillation or flutter occurred in 112 (1·4%) of 8043 patients in the odanacatib group versus 96 (1·2%) of 8028 in the placebo group (HR 1·18, 0·90–1·55; p=0·24). Odanacatib was associated with an increased risk of stroke (1·7% [136/8043] vs 1·3% [104/8028], HR 1·32, 1·02–1·70; p=0·034), but not myocardial infarction (0·7% [60/8043] vs 0·9% [74/8028], HR 0·82, 0·58–1·15; p=0·26). The HR for all-cause mortality was 1·13 (5·0% [401/8043] vs 4·4% [356/8028], 0·98–1·30; p=0·10). When data from LOFT Extension were included, the composite of cardiovascular death, myocardial infarction, or stroke occurred in significantly more patients in the odanacatib group than in the placebo group (401 [5·0%] of 8043 vs 343 [4·3%] of 8028, HR 1·17, 1·02–1·36; p=0·029, as did stroke (2·3% [187/8043] vs 1·7% [137/8028], HR 1·37, 1·10–1·71; p=0·0051). Interpretation Odanacatib reduced the risk of fracture, but was associated with an increased risk of cardiovascular events, specifically stroke, in postmenopausal women with osteoporosis. Based on the overall balance between benefit and risk, the study's sponsor decided that they would no longer pursue development of odanacatib for treatment of osteoporosis