Variable Block Size Research Articles

Alteration and mineralization features of the Akcal Epithermal Gold Deposit, Biga Peninsula, Western Anatolia, Turkey: Evidence for low-sulfidation Au-Ag-Sb mineralization

The Akcal epithermal Au-Ag deposit, located on the Biga Peninsula, southwestern Turkey is estimated to contain 32.5 million tonnes of mineralization at an average grade of 1.03 g/t Au, equivalent to 1.2 million ounces of gold. Epigenetic mineralization is hosted by the lower Miocene Sapci volcanic suite, a calc-alkaline subduction-related volcanic arc consisting mainly of andesitic and basaltic andesitic rocks, while the coeval Soma Formation is composed of sandstone, claystone, conglomerate, marl-limestone, siltstone, and tuffite. Near the base of the volcanic pile, the Karakaya Complex is represented by limestone blocks of various sizes (from a few millimetres to several kilometres) within the Sapci volcanic suite. Short wave infrared (SWIR) and X-ray diffraction (XRD) analyses have shown that kaolinite, illite-smectite, montmorillonite, illite, beidellite, gypsum, vermiculite, quartz, and chlorite are the most common alteration minerals at Akcal. The alteration mineralogy indicates that the temperature of hydrothermal fluids broadly varied from 150° to 230°C, with a mildly acidic pH range of 5.0 to 6.5; these conditions accompanied by a lack of alunite suggest low-sulfidation epithermal conditions for the formation of the Akcal epithermal Au-Ag deposit. Petrographic examination and microanalysis by scanning electron microscopy indicate that mineralization at Akcal consists of pyrite and arsenopyrite with lesser hematite, ilmenite, rutile, and apatite. The occurrence of pyrite and hematite on cleavage planes of hydrothermal biotite is evidence of replacement of an earlier potassic alteration phase. Further petrographic examination of the basal limestone reveals replacement by sulfides displaying complex colloform intergrowths of pyrite and marcasite. The lack of skarn alteration and marble supports a carbonate-replacement origin for sulfides occurring in the basal limestone and is likely related to epithermal mineralization at Akcal. Geochemical results show that an Au-Ag-As-Sb±Pb±Zn signature is dominant across the volcanic-hosted epithermal mineralization and carbonate-replacement occurrences in the basal limestone; the lack of Cu mineralization (< 92 ppm) is typical of low-sulfidation epithermal systems. Strong positive correlations between Au and Ag (r′=0.77), As (0.80), and Sb (0.86) indicate that gold is likely hosted as a sub-microscopic phase within pyrite, arsenian pyrite, and arsenopyrite; visible gold (or free gold) and (or) electrum were not identified at Akcal. A model of fluid mixing involving shallow circulating meteoric waters with deeper magmatic-hydrothermal fluids is proposed for the genesis of gold mineralization at Akcal; a positive Au correlation with Mo (r′=0.74) and Mo concentrations of up to 582 ppm, support the involvement of magmatic-hydrothermal fluids in the epithermal system. Boiling as a mechanism for gold precipitation is unlikely given paleodepths of greater than 250 meters (3.0-5.0 MPa) and model temperatures of 150° to 230 °C. Mineralogical and textural evidence of boiling, such as adularia, bladed calcite, and lattice-texture quartz, have not been observed at Akcal. However, the presence of a silica-rich blanket with chalcedony (at Akcal surface) and having formed near the paleo water table may indicate some involvement of CO 2 – rich steam-heated waters, which could suggest some influence from boiling at depth, although evidence of boiling has not been confirmed in samples from Akcal. Precipitation of gold during the fluid mixing process would have occurred through a shift to higher f O 2 conditions and destabilization Au-thiosulphide complexes. This shift towards higher f O 2 is supported by the occurrence of gypsum and hematite with gold mineralization at depth.

Early integration of palliative care versus standard cardiac care for patients with heart failure (EPCHF): a multicentre, parallel, two-arm, open-label, randomised controlled trial

Heart failure is a substantial global health concern that severely affects patients' quality of life. We aimed to compare the effects of early integration of palliative care (EIPC) and standard cardiac care on health status and mood of patients with non-terminal heart failure. EPCHF was a multicentre, parallel, two-arm, open-label, randomised controlled trial carried out at University Hospital Bonn and University Hospital Düsseldorf in Germany. Eligible patients (aged 18years or older) had heart failure, with New York Heart Association class IIor more and NT-proBNP concentrations greater than or equal to 400pg/mL. Patients were randomly assigned (1:1) to receive EIPC with standard cardiac care or standard cardiac care alone. Randomisation was computer-generated with allocation concealment, variable block sizes, and stratification by investigational site. The primary endpoints were health status and mood, measured every 3months over 12months using the Functional Assessment of Chronic Illness Therapy-Palliative Care (FACIT-PAL) and the Kansas City Cardiomyopathy Questionnaire (KCCQ), analysed by intention to treat. This trial is registered with DRKS.de, DRKS00013922. Between May 21, 2019, and Nov 15, 2021, 843patients were assessed for eligibility, 205of whom were enrolled (100 assigned to EIPC and 105assigned to standard cardiac care). 143 (70%) patients were male and 62 (30%) were female. Over 12months, both groups significantly improved in FACIT-PAL and KCCQ Overall Summary Score(OSS) with no significant differences between the groups (FACIT-PAL adjusted mean difference 0·98points [95% CI -1·28to 3·23]; p=0·40; KCCQ-OSS adjusted mean difference -2·06points [-7·89to 3·78]; p=0·49). Nine (9%) patients in the EIPC group and seven (7%) patients in the standard cardiac care group died from any cause, with no significant differences in time to death between the two groups (hazard ratio [HR] 1·32 [95% CI 0·49 to 3·54]; p=0·58). 22 (22%) patients in the EIPC group and 21 (21%) patients in the standard cardiac care group were hospitalised at least once due to heart failure, with no significant differences in time to heart-failure-related hospitalisation between the two groups (HR 1·09 [0·61 to 1·98]; p=0·77). 70 (70%) patients in the EIPC group and 62 (59%) in the standard cardiac care group had any adverse events (p=0·10). In this open-label, randomised clinical trial, standard cardiac care, featuring guideline-directed optimisation of medical therapy and regular 3-monthly follow-ups was found to be as effective as when combined with EIPC in improving health status and mood in patients with non-terminal heart failure. Future clinical practices should consider EIPC based on individual patient needs. Federal Ministry of Education and Research.

Imprint of a dead-ice environment on lidar imagery—Spatial patterns at the last Scandinavian Ice Sheet margin (N Poland)

There is a unique glacial landscape system in the southern Żarnowiec Moraine Plateau of northern Poland. Here the terrain is characterized by a very high concentration of ridges that are often adjacent to pits, which together constitutes a special type of hummocky topography. The morphological diversity of the study-area ridges and pits was determined from high-resolution lidar imagery that was qualitatively and quantitatively processed, then analysed. Fourteen test fields of spatial dimensions 0.5 km × 0.5 km were selected within the moraine plateau for detailed studies. The results show that the ridges and pits constitute a very dense network of approximately circular, diverse-oriented forms of various sizes, most of which are linked to each other in a step-wise fashion. The pits are surrounded by ridges of various heights and widths that separate one pit from another. A characteristic feature of the studied pits is the orientation of their long axis. Form-based morphological analysis revealed that their genesis was associated with a glacial rather than a periglacial environment. It is believed that ridge orientation reflects a spatial pattern related to ice crevasses. A moraine plateau constituted a terrain obstacle that acted as a counterslope to the advancing ice sheet. The studied landforms and landscape resulted from the ice sheet's breaking up into dead-ice blocks of various sizes. The very dense system of perpendicular, parallel, and diagonal crevasses was related to ice sheet advance from a northerly direction, resulting in a flow around the obstacle and differences in ice-mass speed.

Rapid CU Partitioning and Joint Intra-Frame Mode Decision Algorithm

H.266/Versatile Video Coding (VVC) introduces new techniques that build upon previous standards, proposing a nested multi-type tree quadtree (QTMT). The introduction of this structure significantly enhances video coding efficiency; additionally, the number of directional modes in H.266 has increased by 32 compared to H.265, accommodating a greater variety of texture patterns. However, the changes in the related structures have also led to a significant increase in encoding complexity. To address the issue of excessive computational complexity, this paper proposes a targeted rapid Coding Units segmenting approach combined with decision-making for an intra-frame modes algorithm. In the first phase of the algorithm, we extract different features for CU blocks of various sizes and input them into the decision tree model’s classifier for classification processing, determining the CU partitioning mode to prematurely terminate the partitioning, thereby reducing the encoding complexity to some extent. In the second phase of the algorithm, we put forward an intra-frame mode decision strategy grounded in gradient descent techniques with a bidirectional search mode. This maximizes the approach to the global optimum, thereby obtaining the optimal intra-frame mode and further reducing the encoding complexity. Experimentation has demonstrated that the algorithm achieves a 54.53% reduction in encoding time. In comparison, the BD-BR (Bitrate-Distortion Rate) only increases by 1.38%, striking an optimal balance between the fidelity of video and the efficacy of the encoding process.

Identifying the location and micellization of PEG-b-PCL multiblock copolymers in PLA/PCL blends via AFM nanoscale IR spectroscopy

The IR absorption mapping of two multiblock copolymers based on poly(ethylene glycol) and poly(ε-caprolactone) segments (PEG-b-PCL) in poly(acid lactic) and poly(ε-caprolactone) blends (PLA/PCL) was performed via AFM nanoscale IR spectroscopy. These copolymers, having the same number average molar masses (Mn‾) but varying block sizes, were added into the blend in different amounts (1 and 5 wt%) using a co-rotating twin-screw extrusion. The results revealed that copolymers with smaller blocks are preferentially located near the interface when incorporated in small quantities. Increasing the copolymer content led to preferential diffusion into the PLA matrix. Compatibilization with the longer block-size copolymers also led to preferential diffusion in the PLA matrix, albeit with a tendency to form micelles. This hampers the overall mechanical properties of the blend, making the compatibilized blend more brittle than neat PLA. Compatibilization with the short block-size copolymers showed no micellization and improved the mechanical behavior of PLA/PCL.

Oral resveratrol in adults with knee osteoarthritis: A randomized placebo-controlled trial (ARTHROL).

Resveratrol is a natural compound found in red wine. It has demonstrated anti-inflammatory properties in preclinical models. We compared the effect of oral resveratrol in a new patented formulation to oral placebo for individuals with painful knee osteoarthritis. ARTHROL was a double-blind, randomized, placebo-controlled, Phase 3 trial conducted in 3 tertiary care centers in France. We recruited adults who fulfilled the 1986 American College of Rheumatology criteria for knee osteoarthritis and reported a pain intensity score of at least 40 on an 11-point numeric rating scale (NRS) in 10-point increments (0, no pain, to 100, maximal pain). Participants were randomly assigned (1:1) by using a computer-generated randomization list with permuted blocks of variable size (2, 4, or 6) to receive oral resveratrol (40 mg [2 caplets] twice a day for 1 week, then 20 mg [1 caplet] twice a day; resveratrol group) or matched oral placebo (placebo group) for 6 months. The primary outcome was the mean change from baseline in knee pain on a self-administered 11-point pain NRS at 3 months. The trial was registered at ClinicalTrials.gov: (NCT02905799). Between October 20, 2017 and November 8, 2021, we assessed 649 individuals for eligibility, and from November 9, 2017, we recruited 142 (22%) participants (mean age 61.4 years [standard deviation (SD) 9.6] and 101 [71%] women); 71 (50%) were randomly assigned to the resveratrol group and 71 (50%) to the placebo group. At baseline, the mean knee pain score was 56.2/100 (SD 13.5). At 3 months, the mean reduction in knee pain was -15.7 (95% confidence interval (CI), -21.1 to -10.3) in the resveratrol group and -15.2 (95% CI, -20.5 to -9.8) in the placebo group (absolute difference -0.6 [95% CI, -8.0 to 6.9]; p = 0.88). Serious adverse events (not related to the interventions) occurred in 3 (4%) in the resveratrol group and 2 (3%) in the placebo group. Our study has limitations in that it was underpowered and the effect size, estimated to be 0.55, was optimistically estimated. In this study, we observed that compared with placebo, oral resveratrol did not reduce knee pain in people with painful knee osteoarthritis. ClinicalTrials.gov ID: NCT02905799.

Effect of high versus standard protein provision on functional recovery in people with critical illness (PRECISe): an investigator-initiated, double-blinded, multicentre, parallel-group, randomised controlled trial in Belgium and the Netherlands

Increased protein provision might ameliorate muscle wasting and improve long-term outcomes in critically ill patients. The aim of the PRECISe trial was to assess whether higher enteral protein provision (ie, 2·0 g/kg per day) would improve health-related quality of life and functional outcomes in critically ill patients who were mechanically ventilated compared with standard enteral protein provision (ie, 1·3 g/kg per day). The PRECISe trial was an investigator-initiated, double-blinded, multicentre, parallel-group, randomised controlled trial in five Dutch hospitals and five Belgian hospitals. Inclusion criteria were initiation of invasive mechanical ventilation within 24 h of intensive care unit (ICU) admission and an expected duration of invasive ventilation of 3 days or longer. Exclusion criteria were contraindications for enteral nutrition, moribund condition, BMI less than 18 kg/m2, kidney failure with a no dialysis code, or hepatic encephalopathy. Patients were randomly assigned to one of four randomisation labels, corresponding with two study groups (ie, standard or high protein; two labels per group) in a 1:1:1:1 ratio through an interactive web-response system. Randomisation was done via random permuted-block randomisation in varying block sizes of eight and 12, stratified by centre. Participants, care providers, investigators, outcome assessors, data analysts, and the independent data safety monitoring board were all blinded to group allocation. Patients received isocaloric enteral feeds that contained 1·3 kcal/mL and 0·06 g of protein/mL (ie, standard protein) or 1·3 kcal/mL and 0·10 g of protein/mL (ie, high protein). The study-nutrition intervention was limited to the time period during the patient's ICU stay in which they required enteral feeding, with a maximum of 90 days. The primary outcome was EuroQoL 5-Dimension 5-level (EQ-5D-5L) health utility score at 30 days, 90 days, and 180 days after randomisation, adjusted for baseline EQ-5D-5L health utility score. This trial was registered with ClinicalTrials.gov (NCT04633421) and is closed to new participants. Between Nov 19, 2020, and April 14, 2023, 935 patients were randomly assigned. 335 (35·8%) of 935 patients were female and 600 (64·2%) were male. 465 (49·7%) of 935 were assigned to the standard protein group and 470 (50·3%) were assigned to the high protein group. 430 (92·5%) of 465 patients in the standard protein group and 419 (89·1%) of 470 patients in the high protein group were assessed for the primary outcome. The primary outcome, EQ-5D-5L health utility score during 180 days after randomisation (assessed at 30 days, 90 days, and 180 days), was lower in patients allocated to the high protein group than in those allocated to the standard protein group, with a mean difference of -0·05 (95% CI -0·10 to -0·01; p=0·031). Regarding safety outcomes, the probability of mortality during the entire follow-up was 0·38 (SE 0·02) in the standard protein group and 0·42 (0·02) in the high protein group (hazard ratio 1·14, 95% CI 0·92 to 1·40; p=0·22). There was a higher incidence of symptoms of gastrointestinal intolerance in patients in the high protein group (odds ratio 1·76, 95% CI 1·06 to 2·92; p=0·030). Incidence of other adverse events did not differ between groups. High enteral protein provision compared with standard enteral protein provision resulted in worse health-related quality of life in critically ill patients and did not improve functional outcomes during 180 days after ICU admission. Netherlands Organisation for Healthcare Research and Development and Belgian Health Care Knowledge Centre.

O-017 Swim-up versus density gradients for sperm preparation in intrauterine insemination: a multi-centre randomised clinical trial

Abstract Study question What is the effectiveness of swim-up (SU) and density gradients (DG) for sperm preparation in infertile couples undergoing intrauterine insemination (IUI)? Summary answer In couples undergoing IUI, there is no significant difference in the treatment outcomes between SU and DG. What is known already Swim-up (SU) and density gradients (DG) are the most two commonly used techniques for sperm preparation in intrauterine insemination (IUI). The latest Cochrane review concluded that there is uncertainty about the effectiveness of SU versus DG and no studies reported on live birth. Study design, size, duration This open-label, multi-centre randomised clinical trial was conducted on 912 infertile couples at a tertiary IVF center, Ho Chi Minh City, Vietnam from August 2020 to June 2023. Couples were randomly asigned to two groups, SU and DG using computerized randomisation on the day of IUI with variable block size of 2, 4 or 6. Primary outcome was live birth rate. Participants/materials, setting, methods Infertile couples were eligible if aged ≥18, indicated for IUI with ≤2 IUI prior attempts and husbands’ sperm concentration ≥5x106/ml, progressive motility (PR) ≥32% and total PR sperm count >5x106 before sperm preparation (WHO 2010 criteria). Couples using frozen semen, or high viscosity semen were not eligible. Women had ovulation induction using hMG. Sperm preparation was performed within one hour after ejaculation. IUI was performed once at 36 to 40 hours after hCG trigger. Main results and the role of chance Between August 2020 and June 2023, 912 couples were randomly assigned to SU (n = 456) or DG (n = 456). Baseline characteristics were comparable between the two groups (mean female age of 31.3 ± 0.4 years; total sperm count: 86.2 [52.9;137.6] million; sperm motility: 44.8 ± 8.2%). Live birth occurred in 55 (12.1%) couples in the SU group and 71 (15.7%) couples in the DG group (RR 0.77; 95% CI 0.56-1.07). Ongoing pregnancy and multiple pregnancy were also comparable between the two groups. There were no statistically significant differences between the SU and DG groups with respect to the occurrence of pregnancy complications, obstetric and perinatal complications, preterm delivery, birth weight and neonatal complications. Pre-planned subgroup analysis showed that the live birth rate was not materially affected by the IUI indications, total motile sperm after preparation (<1, ≥1 and <5, ≥5 and <10 and ≥10 million). Limitations, reasons for caution The main limitation of the study was its open-label design, due to the nature of the interventions. Wider implications of the findings Our study suggests that in couples undergoing IUI with progressive motility (PR) ≥32% and total PR sperm count >5x106 before sperm preparation, SU or DG can both be used for sperm preparation, with a preference for density gradients. Trial registration number NCT04477356

Pulmonary Hypertension and Anastrozole (PHANTOM): A Randomized, Double-Blind, Placebo-Controlled Trial.

Inhibition of aromatase with anastrozole reduces pulmonary hypertension in experimental models. We aimed to determine whether anastrozole improved six-minute walk distance (6MWD) at six months in pulmonary arterial hypertension (PAH). We performed a randomized, double-blind, placebo-controlled Phase II clinical trial of anastrozole in subjects with PAH at seven centers. Eighty-four post-menopausal women and men with PAH were randomized in a 1:1 ratio to receive anastrozole 1 mg or placebo by mouth daily, stratified by sex using permuted blocks of variable sizes. All subjects and study staff were masked. The primary outcome was the change from baseline in 6MWD at six months. Using intent-to-treat analysis, we estimated the treatment effect of anastrozole using linear regression models adjusted for sex and baseline 6MWD. Assuming 10% loss to follow-up, we anticipated having 80% power to detect a difference in the change in 6MWD of 22 meters. Forty-one subjects were randomized to placebo and 43 to anastrozole and all received the allocated treatment. Three subjects in the placebo group and two in the anastrozole group discontinued study drug. There was no significant difference in the change in 6MWD at six months (placebo-corrected treatment effect -7.9 m, 95%CI -32.7 - 16.9, p = 0.53). There was no difference in adverse events between the groups. Anastrozole did not show a significant effect on 6MWD compared to placebo in post-menopausal women and men with PAH. Anastrozole was safe and did not show adverse effects. Clinical trial registration available at www. gov, ID: NCT03229499.

Smoking, nicotine and pregnancy 2 (SNAP2) trial: protocol for a randomised controlled trial of an intervention to improve adherence to nicotine replacement therapy during pregnancy

IntroductionSmoking during pregnancy is harmful to unborn babies, infants and women. Nicotine replacement therapy (NRT) is offered as the usual stop-smoking support in the UK. However, this is often used...

Incremental Fuzzy Clustering-Based Neural Networks Driven With the Aid of Dynamic Input Space Partition and Quasi-Fuzzy Local Models.

Fuzzy clustering-based neural networks (FCNNs) based on information granulation techniques have been shown to be effective Takagi-Sugeno (TS)-type fuzzy models. However, the existing FCNNs could not cope well with sequential learning tasks. In this study, we introduce incremental FCNNs (IFCNNs), which could dynamically update themselves whenever new learning data (e.g., single datum or block data) are incorporated into the dataset. Specifically, we employ dynamic (incremental) fuzzy C-means (FCMs) clustering algorithms to reveal a structure in data and divide the entire input space into several subregions. In the aforementioned partition, the dynamic FCM adaptively adjusts the position of its prototypes by using sequential data. Due to the time-sharing arrival of training data, compared with batch learning models, incremental learning methods may lose classification (prediction) accuracy. In order to tackle this challenge, we utilize quasi-fuzzy local models (QFLMs) based on modified Schmidt neural networks to replace the popular linear functions in TS-type fuzzy models to refine and enhance the ability to represent the behavior of fuzzy subspaces. Meanwhile, the recursive least square error (LSE) estimation is utilized to update the weights of QFLMs from one-by-one or block-by-block (fixed or varying block size) learning data. In addition, the L2 regularization is considered to ameliorate the deterioration of generalization abilities caused by potential overfitting when carrying out weight estimation. The proposed method leads to the construction of FCNNs in a new way, which can effectively deal with incremental data as well as deliver sound generalization capability. Extensive machine-learning datasets and a real-world application are employed to show the validity and performance of the presented methods. From the experimental results, we show that the proposal can maintain sound classification accuracy when effectively processing sequential data.

Early postnatal high-dose fat-soluble enteral vitamin A supplementation for moderate or severe bronchopulmonary dysplasia or death in extremely low birthweight infants (NeoVitaA): a multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial

Vitamin A plays a key role in lung development, but there is no consensus regarding the optimal vitamin A dose and administration route in extremely low birthweight (ELBW) infants. We aimed to assess whether early postnatal additional high-dose fat-soluble enteral vitamin A supplementation versus placebo would lower the rate of moderate or severe bronchopulmonary dysplasia or death in ELBW infants receiving recommended basic enteral vitamin A supplementation. This prospective, multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial conducted at 29 neonatal intensive care units in Austria and Germany assessed early high-dose enteral vitamin A supplementation (5000 international units [IU]/kg per day) or placebo (peanut oil) for 28 days in ELBW infants. Eligible infants had a birthweight of more than 400 g and less than 1000 g; gestational age at birth of 32+0 weeks postmenstrual age or younger; and the need for mechanical ventilation, non-invasive respiratory support, or supplemental oxygen within the first 72 h of postnatal age after admission to the neonatal intensive care unit. Participants were randomly assigned by block randomisation with variable block sizes (two and four). All participants received basic vitamin A supplementation (1000 IU/kg per day). The composite primary endpoint was moderate or severe bronchopulmonary dysplasia or death at 36 weeks postmenstrual age, analysed in the intention-to-treat population. This trial was registered with EudraCT, 2013-001998-24. Between March 2, 2015, and Feb 27, 2022, 3066 infants were screened for eligibility at the participating centres. 915 infants were included and randomly assigned to the high-dose vitamin A group (n=449) or the control group (n=466). Mean gestational age was 26·5 weeks (SD 2·0) and mean birthweight was 765 g (162). Moderate or severe bronchopulmonary dysplasia or death occurred in 171 (38%) of 449 infants in the high-dose vitamin A group versus 178 (38%) of 466 infants in the control group (adjusted odds ratio 0·99, 95% CI 0·73-1·55). The number of participants with at least one adverse event was similar between groups (256 [57%] of 449 in the high-dose vitamin A group and 281 [60%] of 466 in the control group). Serum retinol concentrations at baseline, at the end of intervention, and at 36 weeks postmenstrual age were similar in the two groups. Early postnatal high-dose fat-soluble enteral vitamin A supplementation in ELBW infants was safe, but did not change the rate of moderate or severe bronchopulmonary dysplasia or death and did not substantially increase serum retinol concentrations. Deutsche Forschungsgemeinschaft and European Clinical Research Infrastructures Network (ECRIN).

High-dose, short-duration versus standard rifampicin for tuberculosis preventive treatment: a partially blinded, three-arm, non-inferiority, randomised, controlled trial

Tuberculosis preventive treatment (TPT) is a key component of tuberculosis elimination. To improve completion and reduce the burden for people and health systems, short, safe, and effective TPT regimens are needed. We aimed to compare safety and treatment completion of various doses and durations of rifampicin in people who were recommended to receive TPT. This partially blinded, parallel-arm, non-inferiority, randomised, controlled, phase 2b trial was done at seven university-affiliated clinics in Canada, Indonesia, and Viet Nam. Participants aged 10 years or older were included if they had an indication for TPT according to WHO guidelines for Indonesia and Viet Nam, or Canadian guidelines for Canadian sites, and a positive tuberculin skin test or interferon-γ release assay. Participants were randomly assigned (1:1:1) to receive oral rifampicin at 10 mg/kg once daily for 4 months (standard-dose group), 20 mg/kg daily for 2 months (20 mg/kg group), or 30 mg/kg daily for 2 months (30 mg/kg group). The randomisation sequence was computer generated with blocks of variable size (three, six, and nine) and stratified by country for Indonesia and Viet Nam, and by city within Canada. Participants and investigators were masked to dose in high-dose groups, but unmasked to duration in all groups. The two co-primary outcomes were safety (in the safety population, in which participants received at least one dose of the study drug) and treatment completion (in the modified intention-to-treat [mITT] population, excluding those ineligible after randomisation). Protocol-defined adverse events were defined as grade 3 or worse, or rash or allergy of any grade, judged by an independent and masked panel as possibly or probably related to the study. A margin of 4% was used to assess non-inferiority. This study is registered with ClinicalTrials.gov, NCT03988933 (active). Between Sept 1, 2019, and Sept 30, 2022, 1692 people were assessed for eligibility, 1376 were randomly assigned, and eight were excluded after randomisation. 1368 participants were included in the mITT population (454 in the standard group, 461 in the 20 mg/kg group, and 453 in the 30 mg/kg group). 589 (43%) participants were male and 779 (57%) were female. 372 (82%) in the standard-dose group, 329 (71%) in the 20 mg/kg group, and 293 (65%) in the 30 mg/kg group completed treatment. No participants in the standard-dose group, one (<1%) of 441 participants in the 20 mg/kg group, and four (1%) of 423 in the 30 mg/kg group developed grade 3 hepatotoxicity. Risk of protocol-defined adverse events was higher in the 30 mg/kg group than in the standard-dose group (adjusted risk difference 4·6% [95% CI 1·8 to 7·4]) or the 20 mg/kg group (5·1% [2·3 to 7·8]). There was no difference in the risk of adverse events between the 20 mg/kg and standard-dose groups (-0·5% [95% CI -2·4 to 1·5]; non-inferiority met). Completion was lower in the 20 mg/kg group (-7·8% [95% CI -13·6 to -2·0]) and the 30 mg/kg group (-15·4% [-21·4 to -9·4]) than in the standard-dose group. In this trial, 2 months of 30 mg/kg daily rifampicin had significantly worse safety and completion than 4 months of 10 mg/kg daily and 2 months of 20 mg/kg daily (the latter, a fully blinded comparison); we do not consider 30 mg/kg to be a good option for TPT. Rifampicin at 20 mg/kg daily for 2 months was as safe as standard treatment, but with lower completion. This difference remains unexplained. Canadian Institutes of Health Research.

Multicentre, randomised controlled trial of physiological-based cord clamping versus immediate cord clamping in infants with a congenital diaphragmatic hernia (PinC): statistical analysis plan

BackgroundInfants born with congenital diaphragmatic hernia (CDH) are at high risk of respiratory insufficiency and pulmonary hypertension. Routine practice includes immediate clamping of the umbilical cord and endotracheal intubation. Experimental animal studies suggest that clamping the umbilical cord guided by physiological changes and after the lungs have been aerated, named physiological-based cord clamping (PBCC), could enhance the fetal-to-neonatal transition in CDH. We describe the statistical analysis plan for the clinical trial evaluating the effects of PBCC versus immediate cord clamping on pulmonary hypertension in infants with CDH (PinC trial).DesignThe PinC trial is a multicentre, randomised controlled trial in infants with isolated left-sided CDH, born ≥ 35.0 weeks of gestation. The primary outcome is the incidence of pulmonary hypertension in the first 24 h after birth. Maternal outcomes include estimated maternal blood loss. Neonatal secondary outcomes include mortality before discharge, extracorporeal membrane oxygenation therapy, and number of days of mechanical ventilation. Infants are 1:1 randomised to either PBCC or immediate cord clamping using variable random permutated block sizes (4–8), stratified by treatment centre and estimated severity of pulmonary hypoplasia (i.e. mild/moderate/severe). At least 140 infants are needed to detect a relative reduction in pulmonary hypertension by one third, with 80% power and 0.05 significance level. A chi-square test will be used to evaluate the hypothesis that PBCC decreases the occurrence of pulmonary hypertension. This plan is written and submitted without knowledge of the collected data. The trial has been ethically approved.Trial registrationClinicalTrials.gov NCT04373902 (registered April 2020).

Nurse-Led Individualized Follow-Up Versus Regular Physician-Led Visits After Early Breast Cancer (MyHealth): A Phase III Randomized, Controlled Trial.

Follow-up after breast cancer with regular visits has failed to detect recurrences, be cost-effective, and address patient needs. MyHealth is a phase III randomized controlled trial (ClinicalTrials.gov identifier: NCT02949167). Patients, who recently completed primary treatment for stage I-II breast cancer, were randomly assigned in variable block sizes and stratified by age and human epidermal growth factor receptor 2 status to intervention or control follow-up. The nurse-led intervention comprised three to five individual self-management sessions, regular reporting of symptoms, and navigation to health care services. The control follow-up comprised regular outpatient visits with the physician. The primary outcome was breast cancer-specific quality of life (QoL) measured by the Trial Outcome Index-Physical/Functional/Breast summary score of the Functional Assessment of Cancer Therapy-Breast 2 years after random assignment. Secondary outcomes were fear of recurrence, anxiety, depression, and health care utilization. Analyses were intention-to-treat and P values were two-sided with 95% confidence level set at 0.005 because of multiple comparisons. Among 1,101 eligible patients, 875 were invited and 503 were randomly assigned to control (n = 252) or intervention (n = 251) follow-up. At 2 years, patients in the intervention group reported a significantly and clinically relevant higher QoL (mean, 75.69 [standard deviation [SD], 12.27]) than patients in the control group (71.26 [SD, 14.08]), with a mean difference of 5.05 (95% CI, 3.30 to 6.79; P < .001). The intervention group reported significantly less fear of recurrence, anxiety, and depression; they had fewer physician consultations but more nurse contacts and an unchanged diagnostic imaging pattern. The effect on all outcomes was stable through a 3-year follow-up. The MyHealth study suggested a new strategy for follow-up after early breast cancer as it provided significant improvements in QoL.

Efficacy and safety of one anastomosis gastric bypass versus Roux-en-Y gastric bypass at 5 years (YOMEGA): a prospective, open-label, non-inferiority, randomised extension study

The multicentre randomised trial YOMEGA (NCT02139813) comparing the one anastomosis gastric bypass (OAGB) with the Roux-en-Y gastric bypass (RYGB) confirmed the non-inferiority of OAGB on weight loss outcomes at 24 months. We aimed to report weight loss, metabolic, and safety outcomes at 5 years. YOMEGA is a prospective, open-label, non-inferiority, randomised trial conducted at nine centres in France. Inclusion criteria were BMI of 40 kg/m2 or more, or 35 kg/m2 or more with comorbidities. Key exclusion criteria were severe gastro-oesophageal reflux disease or Barrett's oesophagus and previous bariatric surgery. Patients were randomly assigned (1 :1) to OAGB (one gastrojejunal anastomosis with a 200 cm biliopancreatic limb) or RYGB (with a 150 cm alimentary limb and a 50 cm biliary limb), stratified by centre, with blocks of variable size. The primary endpoint of this extension study was percentage excess BMI loss and was analysed in the per-protocol population, including patients with data who were operated on with the technique randomly assigned to them and excluding patients with major deviations from the protocol during the follow-up (change of surgical technique, death, or withdrawal of consent). Non-inferiority was concluded for the primary endpoint if the upper bound of the CI was less than the non-inferiority limit (7 percentage points). YOMEGA is registered with ClinicalTrials.gov, NCT02139813, and the 5-year follow-up of YOMEGA is registered with ClinicalTrials.gov, NCT05549271. Between May 13, 2014, and March 2, 2016, 253 patients were randomly assigned to OAGB (n=129) or RYGB (n=124), and from these patients 114 in the OAGB group and 118 in the RYGB group were included in the per-protocol analysis. In the per-protocol population, at baseline, mean age was 43·0 years (SD 10·8), mean BMI was 44·0 kg/m2 (5·6), 54 (23%) patients were male and 178 (77%) were female; 55 (27%) of 207 patients had type 2 diabetes. After 5 years, mean percentage excess BMI loss was -75·6% (SD 28·1) in the OAGB group versus -71·4% (SD 29·8) in the RYGB group, confirming non-inferiority (mean difference -4·1% [90% CI -12·0 to 3·7], p=0·0099). Remission of type 2 diabetes was similar in both groups. Nutritional status did not differ; the most common adverse event was clinical gastro-oesophageal reflux disease, occurring in 27 (41%) of 66 patients in the OAGB group versus 14 (18%) of 76 patients in the RYGB group (p=0·0030). Among serious adverse events, ten (8%) of 127 patients converted from OAGB to RYGB. 171 (68%) of 253 patients were followed up. OAGB was not inferior to RYGB regarding percentage excess BMI loss at 5 years with similar metabolic outcomes. The high rate of clinical gastro-oesophageal reflux disease after OAGB raises questions about its long-term consequences, which need to be further investigated. Medtronic.

Statistical analysis plan for the Recovery-focused Community support to Avoid readmissions and improve Participation after Stroke randomised controlled clinical trial

BackgroundUnplanned hospital presentations may occur post-stroke due to inadequate preparation for transitioning from hospital to home. The Recovery-focused Community support to Avoid readmissions and improve Participation after Stroke (ReCAPS) trial was designed to test the effectiveness of receiving a 12-week, self-management intervention, comprising personalised goal setting with a clinician and aligned educational/motivational electronic messages. Primary outcome is as follows: self-reported unplanned hospital presentations (emergency department/admission) within 90-day post-randomisation. We present the statistical analysis plan for this trial.Methods/designParticipants are randomised 1:1 in variable block sizes, with stratification balancing by age and level of baseline disability. The sample size was 890 participants, calculated to detect a 10% absolute reduction in the proportion of participants reporting unplanned hospital presentations/admissions, with 80% power and 5% significance level (two sided). Recruitment will end in December 2023 when funding is expended, and the sample size achieved will be used. Logistic regression, adjusted for the stratification variables, will be used to determine the effectiveness of the intervention on the primary outcome. Secondary outcomes will be evaluated using appropriate regression models. The primary outcome analysis will be based on intention to treat. A p-value ≤ 0.05 will indicate statistical significance. An independent Data Safety and Monitoring Committee has routinely reviewed the progress and safety of the trial.ConclusionsThis statistical analysis plan ensures transparency in reporting the trial outcomes. ReCAPS trial will provide novel evidence on the effectiveness of a digital health support package post-stroke.Trial registrationClinicalTrials.gov ACTRN12618001468213. Registered on August 31, 2018.SAP version1.13 (October 12 2023)Protocol version1.12 (October 12, 2022)SAP revisionsNil

Variable Block Size Fractional Motion Estimation Hardware Architecture for VVC and HEVC Standards

The ever-increasing growth in digital video consumption motivates the research and development of new video coding standards to improve coding efficiency. Among the several new tools that the Versatile Video Coding (VVC) standard introduced lies the Quadtree Plus Multi-Type Tree (QT+MTT), which improves upon the quadtree of High Efficiency Video Coding (HEVC) in terms of coding efficiency. Nevertheless, such improvements come at the cost of increased complexity. Hence, to meet the real-time and energy efficiency requirements, embedded devices must adopt techniques to effectively reduce the VVC complexity, including customized hardware accelerators. This work presents a low-energy hardware architecture design for the Fractional Motion Estimation (FME), one of the most critical steps of HEVC and VVC encoders. The proposed architecture supports the Switchable Interpolation Filter (SIF) of VVC and was synthesized to enable Variable Block Size (VBS) from 8×8 up to 128×128 sized blocks so that it can perform the FME of most partitions of the QT+MTT from VVC. The results show increases of at most 4.52% in area and 10.79% in total power for the extra hardware needed to support VBS, and up to 9.15% and 15.72%, in area and power, respectively, for supporting up to 128×128 block sizes.

An efficient hardware architecture of integer motion estimation based on early termination and data reuse for Versatile video coding

The integer motion estimation (IME) involves high computational complexity and large amount of computation data due to the variable block sizes, and it is one of the most critical bottlenecks in video coding. The traditional algorithm for integer motion estimation loses search accuracy when simplifying the motion search process, or it becomes complex to pursue search accuracy, which is not conducive to video encoding and transmission. This paper presents a data reuse algorithm based on search window division, block splitting, the arrangement of search points in the Test Zone (TZ) search algorithm and block division. which divides pixel blocks of different sizes into several 8x8 pixel blocks and then reuses the overlapping 8x8 pixel blocks between adjacent search points of the Test Zone (TZ) search algorithm to reduce hardware resource consumption. By comparing the Sum of Absolute Differences (SAD) values of left and top pixel blocks with current pixel block, the integer motion estimation (IME) can be terminated in advance, reducing the computation complexity of integer motion estimation by over 70 %. Furthermore, the paper also presents a hardware architecture based on the data reuse algorithm, which can process 7680 × 4320@60fps videos at an operating clock frequency of 182.99 MHz, with lower resource consumption compared to similar hardware designs.

A Way to Optimize Delay of Carry-Skip Adders by Using Blocks of Variable Sizes

As one of the most common operational modules in computer processors, the optimization of the propagation delay of adders has attracted extensive attention of researchers. This article proposes a method of optimizing the delay of carry-skip adders by using blocks of variable sizes. By increasing the sizes of the bypass stages gradually and then decreasing it stage by stage, keeping the delay of the first and last stage short, the total propagation delay is optimized. Compared with fixed size carry-skip adders, the delay of variable sizes carry-skip adders has a square root relationship with the number of bits. Thus, when the number of bits is large, the propagation delay is significantly reduced. After calculation, when the number of bits is 16, the propagation delay decreases by 16.67%, and when the number of bits is 256, it decreases by 52.78%. Due to the shorter propagation delay, variable sizes carry-skip adders have faster operation speed and can be applied to improve the performance of computer processors.