Extension Phase Research Articles

Evaluating tibial rotation in recurrent patellar dislocation with four-dimensional computed tomography.

This study is to investigate the three-dimensional (3D) kinematic changes in the knee joint in patients with recurrent patellar dislocation using four-dimensional computed tomography (4DCT) imaging and the 3D-3D surface registration technique. Ten knees from nine patients with recurrent patellar dislocation and seven knees from seven controls (unaffected side of patients with unilateral anterior cruciate ligament injury) were analyzed using 4DCT. The patients were asked to extend their knees from 60° of flexion to full extension for 10s in the CT gantry. We used the 3D-3D registration technique, and the 3D angles of the patella and tibia relative to the femur were evaluated. In the dislocation group, the patellar lateral tilt increased as the knee extended. Significant differences were found between the two groups at 0°-20° of knee flexion. The tibia rotated externally as the knee extended in the dislocation group. Significant differences between the two groups were found at 0°-10° of knee flexion. This study demonstrated significant differences in the timing and magnitude of tibial external rotation between patients with recurrent patellar dislocation and controls. Specifically, the tibia began to externally rotate during the early phase of knee extension in the dislocation group. These findings provide new insights into knee kinematics that may inform future treatment strategies for patellar dislocation.

Development and Validation of Virtual Reality Cognitive Training for Older Adults with Mild Cognitive Impairment: Protocol for a Mixed-Methods Program Evaluation Study.

As research on cognitive training methods for older adults with mild cognitive impairment (MCI) progresses, fully immersive virtual reality cognitive training (fi-VRCT) has shown promise in enhancing cognitive function. However, its effectiveness in improving instrumental activities of daily living (IADL) and fostering independence is still unclear. This study aims to address these uncertainties by developing and validating a fi-VRCT program focused on IADL, with the goal of enhancing both cognitive function and IADL performance in older adults with MCI. This mixed methods program evaluation study consists of three phases: feasibility, intervention, and extension. In the feasibility phase, we will implement fi-VRCT in real-world community settings and invite 20 older adults with MCI to participate in a single training session. Participants will provide feedback through questionnaires and individual interviews. The intervention phase will involve a double-blind, cluster-randomized controlled trial with 52 older adults with MCI, who will be randomly assigned to either the fi-VRCT or control groups. Both groups will complete 16 sessions over eight weeks, with cognitive and functional performance assessed at various intervals. During the extension phase, feedback will be gathered from 26 participants who underwent fi-VRCT through focus group interviews and ongoing questionnaires. Quantitative and qualitative findings will be synthesized to refine the fi-VRCT program and elucidate training outcomes. Ultimately, fi-VRCT has the potential to enhance cognitive and functional abilities in older adults with MCI in community settings. Ethical approval has been obtained from the Research Ethics Committee at National Taiwan Normal University (202312EM009). The research findings will be disseminated through reputable, peer-reviewed journals and professional international conferences to engage and inform academic and clinical audiences. NCT06392412.

Phase reversion mediated the dual heterogeneity of grain size and dislocation density in an equiatomic CrCoNi medium-entropy alloy

An ultra-high strain rate (104 s-1) dynamic plastic deformation treatment at liquid nitrogen temperature (LNT-DPD) followed by annealing is carried out to obtain dual heterogeneity of grain size and dislocation density in an equiatomic CrCoNi medium entropy alloy (MEA). Such extreme loading conditions resulted in extensive phase transformation in this MEA. Subsequent annealing at 650°C for 1 h further induced reverse phase transformation and partial recrystallization, forming a complex heterogeneous microstructure characterized by nested trimodal grain sizes and partitioned dislocation density. A superior yield strength of ∼800MPa and a good ductility of ∼40% were simultaneously achieved in this heterogeneous alloy. In order to reveal the effects of grain size and dislocation density distributions on the mechanical property improvements, the underlying deformation mechanisms were systematically discussed. High density of geometrically necessary dislocations (GNDs) would be induced in complex heterogeneous structures during tensile deformation due to strain gradients or partitioning between different regions, which would lead to additional strengthening and work hardening. These results provide a novel approach to overcome the strength-ductility trade-off dilemma for FCC-structured MEAs.

Safety and efficacy of rodatristat ethyl for the treatment of pulmonary arterial hypertension (ELEVATE-2): a dose-ranging, randomised, multicentre, phase 2b trial

The role of serotonin in pulmonary arterial hypertension has been extensively studied in recent decades, with preclinical data strongly indicating involvement in disease pathogenesis; however, clinical studies have yielded mixed results. ELEVATE-2 was a phase 2b dose-ranging, randomised, double-blind, placebo-controlled, multicentre trial investigating rodatristat ethyl as a treatment for patients with pulmonary arterial hypertension. The study was conducted at 64 sites across 16 countries in Europe and North America. Eligible participants were aged 18 years or older, had pulmonary arterial hypertension with WHO functional class II or III symptom severity, and had received a stable dose and regimen of one or more pulmonary arterial hypertension treatments for at least 12 weeks. Participants were randomly assigned 1:1:1 to receive two placebo tablets, one placebo and one rodatristat ethyl 300 mg tablet, or two rodatristat ethyl 300 mg tablets twice daily using an interactive response system. Participants, investigators, site personnel, and sponsors were masked to treatment allocation. Participants who completed the 24 week treatment period were invited to continue in an open-label extension. The primary endpoint was percent change in pulmonary vascular resistance (PVR) from baseline to week 24. Primary efficacy analyses were conducted on the intention-to-treat population and analyses of harms were conducted in the safety population, which included all patients who received any amount of the study drug. This trial is registered with ClinicalTrials.gov, NCT04712669, and is now complete. Between March 18, 2021 and Dec 13, 2022, 108 participants were enrolled and randomly assigned. 36 participants received placebo, 36 received rodatristat ethyl 300 mg, and 36 received rodatristat ethyl 600 mg twice daily. Overall, 85 (79%) of participants were female and 23 (21%) were male. The mean age was 52·8 years (SD 14·7) in the full analysis set. In the open-label extension phase, 62 (82%) of participants were female and 14 (18%) were male, and the mean age was 52·8 years (SD 14·7); this phase was terminated following sponsor review of unmasked main study results. Least-squares mean percent change in PVR from baseline to week 24 favoured placebo and was 5·8% (SE 18·1) for the placebo group, 63·1% (18·5) for the rodatristat ethyl 300 mg group, and 64·2% (18·0) for the rodatristat ethyl 600 mg group. Treatment-emergent adverse events (TEAE) were reported for 29 (81%) patients in the placebo group, 33 (92%) patients in the rodatristat ethyl 300 mg group, and all 36 (100%) patients in the rodatristat ethyl 600 mg group. TEAE leading to study discontinuation were reported for three (8%) patients in the placebo group, four (11%) patients in the rodatristat ethyl 300 mg group, and four (11%) in the rodatristat ethyl 600 mg group. There was one (3%) TEAE leading to death in the rodatristat ethyl 300 mg group. Our results indicate that reducing peripheral serotonin concentrations via rodatristat ethyl has a negative effect on pulmonary haemodynamics and cardiac function in patients with pulmonary arterial hypertension. This finding suggests that manipulating this pathway might not be a suitable option for pulmonary arterial hypertension therapy. Enzyvant Therapeutics (now Sumitomo Pharma America).

Comparison Between InterCriteria and Correlation Analyses over sEMG Data from Arm Movements in the Horizontal Plane

InterCriteria analysis (ICrA) and two kinds of correlation analyses, Pearson (PCA) and Spearman (SCA), were applied to surface electromyography (sEMG) signals obtained from human arm movements in the horizontal plane. Ten healthy participants performed ten movements, eight of which were cyclic. Each cyclic movement (CM) consisted of flexion and extension phases with equal duration (10 s, 6 s, 2 s, and 1 s) and two 5 s rest poses between them. The CMs were performed with and without an added load of 0.5 kg on the wrists of the participants. The sEMG signals from six different muscles or separate muscle heads (m. deltoideus pars clavicularis, m. deltoideus pars spinata, m. brachialis, m. anconeus, m. biceps brachii, and m. triceps brachii long head) were recorded and used to compare the results of the ICrA, PCA, and SCA. All three methods found identical consonance pairs for the flexion and extension CM phases. Additionally, PCA detected two more consonance pairs in the extension phases. In this investigation, ICrA, PCA, and SCA were proven to be reliable tools when applied separately or in combination for sEMG data. These three methods are appropriate for researching arm movements in the horizontal plane and experimental protocol revision.

Neuromuscular synergy characteristics of Tai Chi leg stirrup movements: optimal coordination patterns throughout various phases.

To investigate the neuromuscular activity characteristics of Tai Chi athletes and identify optimal muscle synergy patterns. Data were collected from 12 elite Tai Chi athletes using a Vicon motion capture system, a Kistler 3D force plate, and a Noraxon surface electromyography system. Muscle synergy patterns were extracted using Non-negative Matrix Factorization. Four muscle synergy patterns were identified in each of the three phases of the leg stirrup movement, with the optimal synergy pattern for each phase determined as follows: knee lift phase: rectus femoris and vastus lateralis of the right leg; extension phase: rectus femoris, vastus lateralis, biceps femoris, and medial gastrocnemius of the right leg; recovery phase: rectus femoris, vastus lateralis, and medial gastrocnemius of the right leg. These patterns explain the muscle coordination activities for each phase. This study identified the optimal muscle synergy patterns for each phase, supporting the fluidity and force generation of the leg stirrup movement. This provides Tai Chi athletes with a more efficient way to exert strength and maintain balance.

The Indosinian Granitoids of the Songpan–Garze–West Kunlun Orogenic Belt, China: Distribution, Petrochemistry, and Tectonic Insights

During the Indosinian orogeny, the Songpan–Garze–West Kunlun orogenic belt experienced significant tectonic and magmatic activity, leading to the widespread emplacement of granitoid bodies. This study provides a detailed petrochemical and geochemical analysis of these granitoids, offering new insights into their tectonic settings and magmatic evolution. The granitoids of this belt are systematically categorized into arc calc-alkaline and arc tholeiitic granitoids (ACG and ATG), cordierite peraluminous and muscovite peraluminous granitoids (CPG and MPG), potassium calc-alkaline granitoids (KCG), and peralkaline granitoids (PAG) suites. ACG and ATG types dominate early magmatism (230–190 Ma), reflecting a convergent tectonic setting, while KCG and MPG types magmatism, respectively, emerged 10–20 Myr and 15–25 Myr later, during post-collisional extensional phases. Geochemical analyses show that ACG and ATG granitoids follow calcic and calc-alkalic trends, while KCG and MPG display alkalic characteristics. These findings align with the region’s tectonic transition from the closure of the Paleo–Tethys Ocean to Late Triassic transpressional deformation. This study enhances the understanding of granitoid petrogenesis and provides valuable implications for regional tectonic evolution and mineral exploration.

The Interplay of Knowledge Management, E-Governance, and Business Performance Efficiency: Insights from Saudi Public Sector Institutions

This study goes more deeply into the critical aspects of understanding knowledge management, e-governance, and performance efficiency in the Saudi public sector. Simultaneously, the main target is first to grasp how these aspects influence this kind of effectiveness, especially in light of this significant Vision 2030 of the State. By utilizing a technique, the research exploited determined it utilitarian of SMART PLS software to model Structural Equation Modeling (SEM) structure. The study involved 170 people, from the highest-level executives to entry-level employees and cross-section management, administration, and IT specialists. The given article will pursue the complexity of the characters’ interactions while revealing some of the book’s central lessons. T for this study tool, an elaborate questionnaire went through an extensive pretest phase where the content validity and reliability were verified through interviews with expert methods. In 2023, over a quarter of a year data collection period, the self-administered questionnaire was distributed to the representatives of different public institutions, which was done during the year 2023. We obtained some necessary information through the data found and processed using the SMART PLS and SEM. Outcomes highlighted the complex and multidimensional interrelationship of knowledge management, e-governance, and business performance efficiency, from which we make the knowledge of various factors facilitating the performance of the public sector offices in Saudi Arabia. Indeed, it is worth mentioning that the research endorses essential elements in line with Vision 2030, adding tangible directions to the policymakers, government leaders, and practitioners aiming to increase the productivity and effectiveness of public sector projects in the Kingdom.

Eighteen-Month Hybrid Closed-Loop Use in Very Young Children With Type 1 Diabetes: A Single-Arm Multicenter Trial.

We aimed to evaluate the longer-term safety and efficacy of hybrid closed-loop (CL) therapy in very young children with type 1 diabetes (T1D). Following a 16-week multinational, randomized crossover trial comparing hybrid CL with sensor-augmented pump (SAP) therapy in 74 very young children aged 1-7 years with T1D, participants were invited to an extension phase using CL for a further 18 months. Outcomes were compared with the primary-phase SAP period and primary-phase CL period. After the primary study phase, 60 participants were eligible to enroll in the extension. Of these, 49 consented (mean ± SD age 6.6 ± 1.5 years) to continue use of CL for 18 months. Percentage time in range (TIR) 3.9-10.0 mmol/L was 8.4 percentage points (95% CI 6.7 to 10.1; P < 0.001) higher, while HbA1c was 0.4% ([5.0 mmol/mol], 95% CI 0.3 to 0.6 [3.7 to 6.2]; P < 0.001) lower during the CL extension phase compared with primary-phase SAP period. At 18 months, mean HbA1c was 6.7 ± 0.5% and TIR was 70 ± 7%, compared with 6.7 ± 0.5% and 71 ± 6% in the primary-phase CL period. Time in hypoglycemia (<3.9 mmol/L) was similar between CL extension phase and both primary-phase SAP (P = 0.31) and CL periods (P = 0.70). There were two severe hypoglycemia events and one other serious adverse event during the extension phase. One unexpected serious adverse device effect occurred. Use of the Cambridge hybrid CL system led to sustained improvements in glycemic control lasting more than 18 months in very young children with T1D.

Exploring Piperine: Unleashing the multifaceted potential of a phytochemical in cancer therapy.

Radiotherapy is a cornerstone in the treatment of solid tumors, with extensive Phase III trials confirming its effectiveness. As advancements in treatment technologies and our understanding of tumor resistance mechanisms continue, the role of radiation oncology is set to become even more pivotal. Addressing the global challenge of lethal cancers demands innovative strategies, particularly in minimizing the side effects associated with traditional chemotherapy and ionizing radiation (IR). Recently, there has been growing interest in natural compounds for radioprotection, aiming to prevent tumor development and metastasis. Piperine, a compound found in black and long pepper, has emerged as a promising chemopreventive agent that works effectively without harming normal cells. Mechanistically, piperine modulates key signaling pathways, inhibits cancer cell migration and invasion, and enhances sensitivity to IR. Combining piperine with radiotherapy offers a compelling approach, boosting treatment efficacy while protecting healthy tissues from radiation damage. Piperine's versatile role goes beyond radiosensitization to include radioprotection by inhibiting NF-κB activation, reducing autophagy, and promoting apoptosis in cancer cells. This dual action makes it a promising candidate for personalized cancer care. As research advances, the therapeutic potential of piperine may drive new frontiers in cancer treatment strategies.

Glycaemic outcomes in adults with type 2 diabetes over 34 weeks with the Omnipod® 5 automated insulin delivery system.

The aim was to evaluate the effect of extended use of the Omnipod® 5 automated insulin delivery (AID) system in adults with type 2 diabetes and suboptimal glycaemic control. Following an 8-week single-arm, multicentre, outpatient trial of AID in adults with type 2 diabetes and baseline ≥ 64 mmol/mol, participants were given the opportunity to continue use of the AID system in a 26-week (~6 month) extension phase. The primary safety endpoints were percentage of time with sensor glucose ≥ 250 mg/dL and < 54 mg/dL. Additional glycaemic measures, including percentage of time in range (TIR) (70-180 mg/dL) and HbA1c, were evaluated. The use of non-insulin anti-hyperglycaemic medications was permitted throughout the entire study. During the initial 8-week study, participants (N = 22) achieved a decrease in percentage of time ≥ 250 mg/dL from 27.4% ± 21.0% to 10.5% ± 8.8% (p < 0.0001), which further decreased to 9.7% ± 9.2% during the extension phase (p = 0.0002 vs. standard therapy). Percentage of time < 54 mg/dL remained low from standard therapy through extension (median [interquartile range] 0.00% [0.00%, 0.06%] vs. 0.02% [0.00%, 0.05%], p > 0.05). HbA1c decreased by 1.6% ± 1.2% (15.5 ± 13.1 mmol/mol, p < 0.0001) and TIR increased by 22.4% ± 19.2% (p < 0.0001) from standard therapy through extension with no significant change in body mass index and without an observed increase in total daily insulin requirements. These longer-term findings of Omnipod 5 AID system use demonstrate the potential value of AID in helping people with type 2 diabetes reach glycaemic targets.

Cross-cultural adaptation and psychometric properties of the Chinese version of the Intermittent Self-Catheterization Questionnaire (ISC-Q).

The intermittent self-catheterization questionnaire (ISC-Q) is a valid and reliable tool to assess the quality of life (QOL) in patients with neurogenic lower urinary tract dysfunction (NLUTD) who engage in ISC. The aim of this research is to culturally adapt the ISC-Q and evaluate its psychometric properties within the Chinese patient population. The cross-sectional research was meticulously conducted in two pivotal stages: initially, the focus was on cross-cultural adaptation, followed by an extensive phase of psychometric testing. This comprehensive analysis involved 405 Chinese patients with NLUTD who use ISC. Various analyses, including evaluations of the floor and ceiling effects, item analysis, content validity, exploratory and confirmatory factor analysis (EFA and CFA), assessments of convergent, discriminant, and criterion validity. Additionally, Cronbach's alpha was utilized to determine internal consistency, and test-retest reliability was measured using the intraclass correlation coefficient (ICC). No floor and ceiling effects were observed. The content validity index was 0.967. The EFA identified four factors, accounting for 64.953% of the total variance, and this four-factor structure was confirmed by the CFA. The fit indices in CFA were favorable, with χ2/df = 1.999, root mean square error of approximation = 0.070, comparative fit index = 0.916, Tucker-Lewis index = 0.900, goodness-of-fit index = 0.863, and incremental fit index = 0.917. The average variance extracted for the four factors ranged from 0.466 to 0.565, with composite reliability values ranging from 0.776 to 0.859. The ISC-Q showed a positive correlation with the intermittent self-catheterization acceptance questionnaire (r = 0.557, P < 0.001). The ICC overall Cronbach's alpha coefficient for the questionnaire was 0.821, and the for test-retest reliability was 0.951 (95% CI [0.900-0.976] P < 0.001). The validity and reliability of the Chinese version of the ISC-Q have been verified, making it suitable for measuring the QOL in NLUTD patients who practice ISC.

Late Cambrian-early Ordovician extensional magmatism, uplift and sedimentation of the N Gondwana margin: new field, geochemical and geochronological data from the peri-Gondwanan Central Sakarya Terrane, Sakarya Zone, NW Turkey

ABSTRACT The timing and mechanism of the crustal extension that caused blocks of continental crust to rift and drift northwards from the northern Gondwana margin during the Early Palaeozoic are currently debated. Here, we present new field, geochemical and U-Pb zircon data from peri-Gondwanan Central Sakarya terrane in NW Turkey to shed light on the timing and petrogenesis of extensional magmatism and subsequent passive margin development of the northern Gondwana margin. Our 1/25.000 scale mapping of a selected area (250 km2) has revealed a south-vergent thrust stack comprising three slices. The Middle Slice of the thrust stack consists of a gneiss-amphibolite complex that has a basement-cover type stratigraphy (before regional metamorphism). The basement unit consists of meta-granitoids, intruded by meta-syenite and banded amphibolites, with geochemical characteristics reflecting I&S-type, A-type and within plate alkaline/transitional-type magmatism, respectively. The cover meta-clastic sediments have amphibolite lenses with MORB and back-arc basin-type geochemistry. Meta-granitoid bodies yielded zircon U-Pb ages of 507 ± 16 Ma, 503 ± 12 Ma, and 488 ± 2.6 Ma (Late Cambrian-Early Ordovician), whereas the meta-syenites gave ages of 473.9 ± 5.7 Ma and 471.4 ± 2.5 Ma (late Early Ordovician); also, age of the banded amphibolite was dated as 473.3 ± 4 Ma. The youngest detrital zircon population in the pebbly quartzite sample within cover meta-sediments (458 ± 3 Ma) constrains the maximum depositional age to around early Late Ordovician. The late Early Ordovician bimodal magmatism, a key focus of our study, is interpreted to have formed in response to the Rheic Ocean rifting along the northern margin of Gondwana. The Late Cambrian granitic magmatism, a precursor to bimodal magmatism, can be explained by lithospheric thinning and upwelling of the asthenosphere to form anatectic silicic melts. The unconformity between the basement and cover units may represent the initiation of a new phase of extension at the N Gondwana margin that culminated in the northward drifting of the Central Sakarya and the opening of Palaeotethys, associated with back-arc basic magmatism in Late Ordovician-Silurian.

Relative muscular effort in the older adults during the sit-to-stand task: Monitoring neuromuscular reserve and movement limitations

BackgroundDue to lower maximum strength, older adults purportedly need to exert greater muscular effort to stand up from a chair. This study investigated joint-specific muscular effort during a sit-to-stand by calculating relative-muscular-effort and investigating differences between healthy older and young adults. MethodsFifteen older (age: 69.9 ± 3.5 years) and 15 young (age: 22.2 ± 2.6 years) adults performed five self-paced sit-to-stand trials. Kinematic and kinetic data were collected and used to calculate inverse dynamics net joint moment. Peak isometric knee and hip extensor torques were measured and used as inputs to regression models that predicted angle- and velocity-dependent maximum potential net joint moment. Knee and hip relative-muscular-effort were calculated as the net joint moment during the task and their maximum capacity. FindingsKnee and hip extensor relative-muscular-effort did not differ between age groups during momentum-transfer and extension phases of the sit-to-stand. However, peak knee and hip moments during the sit-to-stand, knee and hip maximum potential moments as well as peak knee and hip torques were significantly lower in older adults compared to young adults. InterpretationAlthough there were age-related decreases in muscle strength and joint kinetics during the sit-to-stand task in older adults, the findings that older adults exhibited similar knee and hip relative-muscular-effort to young adults suggests that neither knee nor hip extensors operated close to their maximum capacity during this task. Therefore, neuromuscular reserve in knee and hip strength may not be a critical limiting factor for healthy older adults during the two phases of sit-to-stand.

Continuous glucose monitoring-based metrics and the duration of hypoglycaemia events with once-weekly insulin icodec versus once-daily insulin glargine U100 in insulin-naive type 2 diabetes: an exploratory analysis of ONWARDS 1

Continuous glucose monitoring (CGM) can provide a comprehensive assessment of glycaemic control. This exploratory analysis of the ONWARDS 1 trial assessed CGM-based metrics and CGM-derived hypoglycaemia duration in insulin-naive individuals with type 2 diabetes treated with subcutaneous once-weekly insulin icodec (icodec) versus once-daily insulin glargine U100 (glargine U100). ONWARDS 1 was a 78-week (52-week main treatment phase and a 26-week treatment extension phase plus a 5-week follow-up), randomised, open-label, treat-to-target, phase 3a trial done at 143 sites (outpatient clinics and hospital departments) across 12 countries. Adults (aged ≥18 years) with type 2 diabetes (HbA1c: 7·0-11·0%) who had not previously received insulin were randomly assigned (1:1) via an interactive web-response system to once-weekly icodec or once-daily glargine U100. Double-masked CGM data were collected during treatment initiation (weeks 0-4), midtrial (weeks 22-26), end of main phase (weeks 48-52), end of extension phase (weeks 74-78), and follow-up (weeks 78-83). Secondary and exploratory outcomes were CGM-based metrics, including the mean percentages of time in glycaemic range (TIR; sensor glucose 3·9-10·0 mmol/L [70-180 mg/dL]), time in tight range (TITR; 3·9-7·8 mmol/L [70-140 mg/dL]), time above range (TAR; >10·0 mmol/L [>180 mg/dL]), and time below range (TBR; <3·9 mmol/L [<70 mg/dL] and <3·0 mmol/L [<54 mg/dL]), and CGM-derived hypoglycaemic episode durations (episodes defined by sensor glucose <3·9 mmol/L [<70 mg/dL for ≥15 consecutive minutes]). Analyses were done in the full analysis set (all randomly assigned participants). The ONWARDS 1 trial is registered with ClinicalTrials.gov, NCT04460885, and is complete. Participants were enrolled and randomly assigned in ONWARDS 1 between Nov 25, 2020, and Dec 1, 2022 (n=492 in each treatment group). During treatment initiation, we observed no statistically significant differences in the mean percentages of TIR, TITR, TAR, and TBR with icodec versus glargine U100. During the midtrial, end of main phase, and end of extension phase periods, the mean percentages of TIR and TITR were statistically significantly greater and the mean percentages of TAR statistically significantly lower with icodec versus glargine U100. The mean percentages of TIR met the internationally recommended CGM target (>70%) with icodec but not with glargine U100 during the three periods. TBR (<3·9 mmol/L [<70 mg/dL] and <3·0 mmol/L [<54 mg/dL]) was low and below recommended targets (<4% and <1%, respectively) across all study periods in both treatment groups, with no statistically significant differences between treatment groups for the lower threshold (<3·0 mmol/L [<54 mg/dL]). During the follow-up period, mean percentages of TIR, TITR, TAR, and TBR did not statistically significantly differ with icodec versus glargine U100. The duration of overall hypoglycaemic episodes was similar between treatment groups throughout the trial (median duration ≤35 min). These CGM data support the long-term efficacy and safety of icodec versus glargine U100 during treatment and indicated no increase in the duration of individual hypoglycaemic episodes with icodec versus glargine U100 in insulin-naive individuals with type 2 diabetes. Novo Nordisk.

Efficacy and safety of pasireotide treatment in acromegaly: A systematic review and single arm meta-analysis.

Acromegaly is a rare chronic endocrine disorder associated with significant comorbidities. Many patients fail to achieve biochemical control with current medical therapies, including surgery and first-generation somatostatin ligands (fg-SRLs). We aimed to perform a systematic review and single-arm meta-analysis to evaluate the efficacy of the multi-receptor somatostatin ligand pasireotidein patients with active or uncontrolled acromegaly. We systematically searched PubMed, Embase, and Cochrane databases for studies that assessed the efficacy of pasireotide in patients withacromegaly and reported the outcomes of (1)biochemical control and its composite indicators; (2)normalized IGF-1 level and (3)low GH level.For the statistical analysis, we used R software. We included nine studies with a total of 590 patients: four clinical trials and five observational cohorts. 82.2% of the overall population consisted of inadequately controlled acromegaly patients. After a follow-up of 12months, the pooled biochemical control rate was 26.50% (95% CI 14.87-42.66). The prevalence of normalized IGF-1 and low GH levels was 36.27% (95% CI 29.15-43.39) and 34.76% (95% CI 24.58-44.95), respectively. Additionally, biochemical response rates were sustained throughout the extension phase of these studies. In a pooled analysis including four studies with extension phase results, the prevalence of biochemical control rate was 29.03% (95% CI 11.49-46.58) with 76 events out of 281 patients. The most commonly reported adverse events were gastrointestinal disturbances in 31.26% (95% CI 7.44-72.01) and hyperglycemia in 29.55% (95% CI 21.80-37.29) of patients. The incidence of new-onset diabetes mellitus significantly increased after pasireotide treatment, with a rate of 23.36% (95% CI 19.58-27.13). Pasireotide demonstrates biochemical control in patients with active or uncontrolled acromegaly. Although a high rate of hyperglycemic adverse events and diabetes mellitus related to the treatment were observed, most of them were manageable.

Tectonostratigraphic framework and provenance of a Mesoproterozoic rift succession: An example from the Espinhaço Supergroup, SE Brazil

During the Mesoproterozoic era, the amalgamation of the Rodinia supercontinent witnessed numerous intraplate rifting events far-field induced by “Grenvillian-type age” orogenic systems. The intimate connection between tectonics and sedimentation enables the reconstruction of these intraplate rifting cycles, linking them to accretionary events along craton margins. This is essential for understanding the paleotectonic history of continents during the Mesoproterozoic era. In southeastern Brazil, the Espinhaço Supergroup documents long-lasting superimposed rifting events that extended to the eastern border of the São Francisco paleocontinent from the Paleoproterozoic to the Mesoproterozoic era. Three unconformity-bound rift sequences (∼1.77–1.7 Ga; ∼1.57–1.5 Ga; and ∼ 1.19 Ga) have been identified within the Espinhaço Supergroup, terminated by sag-marine deposits of the Conselheiro Mata Group. In the southern extension of the southern Espinhaço range (Cipó range), a detailed sedimentological and stratigraphic study was conducted on a rift-related sequence with unknown stratigraphic positioning. This sequence is bounded at the base by eolian sediments of the Galho do Miguel Formation of the Southern Espinhaço Supergroup and at the top by Ediacaran-Cambrian carbonates and pelites of the Bambuí Group. Examination of the tectonically-induced depositional controls in the provenance signatures involved stratigraphic surveys coupled with U-Pb geochronological data of detrital zircons. The lower section of the rift-related sequence transitions eastward into marine sediments of the Conselheiro Mata Group within the Santa Rita Formation, now identified as the Lower Member. With a maximum depositional age of 1660 ± 32 Ma, this section directly overlies the Galho do Miguel Formation by an erosive unconformity, comprising syn-rift coarse-grained deposits from alluvial and fluvial systems within an inverted half-graben structure. The Lower Member of the Santa Rita Formation provides evidence of the Mesoproterozoic rifting event associated with the Conselheiro Mata Group. The marine sediments of the Undefined sequence have a maximum depositional age of 1462 ± 19 Ma, overlying the Lower Member of the Santa Rita Formation with an erosive unconformity. The stratigraphic position of this sequence remains speculative, possibly linked to a later extensional phase of the Mesoproterozoic Conselheiro Mata rifting event or one of the two continental rifting stages leading to the Neoproterozoic Macaúbas Group.

New Mesozoic APWP for Adria aided by data from the Transdanubian Range Unit – Tectonic interpretation in the Europe – Africa geodynamic system

Mesozoic paleomagnetic data from the Transdanubian Range Unit (TRU) of the Pannonian Basin has been revised and updated to enable its paleogeographic evolution within SE Europe to be evaluated. After a 30° declination correction, the TRU data are fully consistent with those for Adria which has an almost identical stratigraphic history. This enabled a revised Apparent Polar Wander Path (APWP) to be constructed for the combined data. Comparing this with the corresponding African and European APWP shows that Adria separated from Europe around 190 Ma, then moved independently southwards between 170–120 Ma (a 30° clockwise rotation changing to counter-clockwise around 155–145 Ma). After 155 Ma, there was a northward movement that brought Adria close to the stable European margin by 115 Ma. This latter may have been with or independently of Africa. After 100 Ma, Africa and Adria moved in coordination until the end of the Cretaceous. This sequence of events correlated well with geologically established tectonic events. These include the major extensional phases in the Alpine Tethys during the southward shift and large clockwise rotation (170–155/145 Ma). This was followed by ophiolite obduction in the Neotethys (West and East Vardar) around 155–145 Ma as a result of the dramatic reversal in the displacement of Adria. Finally, around 115 Ma, the TRU was emplaced over Austroalpine units as a thick nappe associated with the general uplift in the Adriatic realm.

Comparing outcomes of patients with early active rheumatoid arthritis initially treated on an inpatient or outpatient basis: a posthoc analysis of the CORRA trial

ObjectiveTreatment strategies of patients with active rheumatoid arthritis (RA) vary within and between countries. While most patients in Germany are treated on an outpatient basis, some are hospitalised (inpatients). In...

Petrogenesis and tectonic implication of the Triassic monzogranite from the central segment of the East Kunlun Orogen, NW China

The Triassic granitoids in the East Kunlun Orogenic Belt (EKOB) are crucial for understanding the tectonic evolution of the Paleo-Tethys Ocean. This study presents zircon U–Pb ages, Lu–Hf isotopes, whole-rock major and trace elements, and Sr–Nd isotope compositions from monzogranite plutons in the central segment of EKOB to constrain their petrogenesis and tectonic evolution. These monzogranites are dominant composed of mineral assemblages of K-feldspars, plagioclase, minor biotite and accessory minerals. U–Pb dating of zircons from the Xinle South (XLS), Nanshankou (NSK) and Changgou South (CGS) plutons yield ages of 251 Ma, 232 Ma and 221 Ma, respectively. The studied monzogranites have relatively high SiO2 and Al2O3, but have low contents of TiO2, Fe2O3T, MgO relative to the coeval granodiorites. These monzogranites are classified as fractionated I-type granites, ranging from calc-alkaline to high-K calc-alkaline compositions. Their negative εNd(t) values (−4.2 to −6.3) and zircon εHf(t) values (−6.1 to −9.3) suggest that magma generation occurred through partial melting of ancient lower crust, followed by extensive fractional crystallization. Integrating our new data with regional geological evidence, we propose that the Early Triassic XLS monzogranite emplaced in a localized extensional environment linked to the northward subduction of the Paleo-Tethys oceanic plate. In contrast, during the post-collisional extensional phase of the Late Triassic, the formation of the NSK and CGS monzogranite plutons was directly influenced by asthenospheric upwelling, lower crust delamination, and subsequent continental rifting.