Assessment Period Research Articles

Effect of clinician's experience and expertise on the inter- and intra-observer reliability of the computed tomography-based classification systems in posterior malleolus fractures.

Three computed tomography (CT)-based classifications, including Haraguchi, Bartoníček-Rammelt, and Mason-Molloy systems, have been developed to better determine the characteristics of posterior malleolus fractures (PMFs). The aims of this study were (1) to determine the intra- and inter-observer reliability of the computed tomography-based classification systems and (2) to investigate the clinical experience and expertise on their reliabilities. Sixty-seven preoperative ankle CT scans of 67 adult patients with "ankle fracture with the involvement of the posterior malleolus"'' were retrospectively identified. CT images were assessed by 10 observers with different levels of clinical experience from 2 different specialties, including orthopedics and radiology. The observers were asked to classify PMFs according to 3 CT-based classifications on 2 separate occasions with a 4-week interval. Cohen's κ values were measured for 2 raters and Fleiss' κ values were measured for 3 raters and more. Overall, each classification had moderate to very good intraobserver reliability (κ=0.41 to 0.95, P < .01) as well as moderate interobserver reliability for each of the 2 separate assessments (κ=0.41 to 0.60, P < .01 for the first occasion; κ=0.44 to 0.59, P < .01 for the second occasion). Interobserver agreement among the foot and ankle surgeons regarding the Haraguchi and Bartoníček classifications was substantial for both assessment periods, whereas there was a moderate agreement for the Mason classification. Orthopedic residents showed moderate interobserver agreement in each period for both Bartoníček and Mason classifications. Radiology experts illustrated slight and fair agreements in the 2 assessments for Mason classification, moderate agreement in both assessments for Haraguchi classification, and substantial to moderate agreement in the first and second assessments for Bartoníček classification, respectively. Computed tomography-based classification system for PMFs demonstrated moderate interobserver reliability as well as moderate to very good intraobserver reliability. Moreover, foot and ankle specialists exhibit enhanced K values for both inter and intraobserver reliability for each classification system, consistency seems to increase as the interest in the field condenses.

Fixed-duration pirtobrutinib plus venetoclax with or without rituximab in relapsed/refractory CLL: the phase 1b BRUIN trial

AbstractPirtobrutinib is a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor (BTKi). Patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) were treated with fixed-duration pirtobrutinib plus venetoclax (PV) or pirtobrutinib plus venetoclax and rituximab (PVR) in this phase 1b trial. Prior covalent BTKi therapy was allowed, but not prior treatment with venetoclax. Patients were assigned to receive PV (n = 15) or PVR (n = 10) for 25 cycles. Most patients (68%) had received prior covalent BTKi therapy. At the data cutoff date, the median time on study was 27.0 months for PV and 23.3 months for PVR. Overall response rates were 93.3% (95% confidence interval [CI], 68.1-99.8) for PV and 100% (95% CI, 69.2-100.0) for PVR, with 10 complete responses (PV: 7; PVR: 3). After 12 cycles of treatment, 85.7% (95% CI, 57.2-98.2) of PV and 90.0% (95% CI, 55.5-99.7) of PVR patients achieved undetectable minimal residual disease (<10-4) in peripheral blood. Progression-free survival at 18 months was 92.9% (95% CI, 59.1-99.0) for PV patients and 80.0% (95% CI, 40.9-94.6) for PVR patients. No dose-limiting toxicities were observed during the 5-week assessment period. The most common grade ≥3 adverse events (AEs) for all patients included neutropenia (52%) and anemia (16%). AEs led to dose reduction in 3 patients and discontinuation in 2. In conclusion, fixed-duration PV or PVR was well tolerated and had promising efficacy in patients with R/R CLL, including patients previously treated with a covalent BTKi. This trial was registered at www.clinicaltrials.gov as #NCT03740529.

Expert Panel Recommendations for a Standardized Ambulatory Glucose Profile Report for Connected Insulin Pens.

Connected insulin pens capture data on insulin dosing/timing and can integrate with continuous glucose monitoring (CGM) devices with essential insulin and glucose metrics into a single platform. Standardization of connected insulin pen reports is desirable to enhance clinical utility with a single report. An international expert panel was convened to develop a standardized connected insulin pen report incorporating insulin and glucose metrics into a single, clinically useful report. An extensive literature review and identification of examples of current connected insulin pen reports was performed serving as the basis for creation of a draft of a standardized connected insulin pen report. The expert panel participated in three virtual standardization meetings and online surveys. The AGP Report: Connected Insulin Pen brings all clinically relevant CGM-derived glucose and connected insulin pen metrics into a single simplified two-page report. The first page contains the time in ranges bar, summary of key insulin and glucose metrics, the ambulatory glucose profile (AGP) curve, and detailed basal (long-acting) insulin assessment. The second page contains the bolus (mealtime and correction) insulin assessment periods with information on meal timing, insulin-to-carbohydrate ratio (ICR), average bolus insulin dose and number of days with bolus doses recorded. The report's second page contains daily glucose profiles with an overlay of the timing and amount of basal and bolus insulin administered. The AGP Report: Connected Insulin Pen is a standardized clinically useful report that should be considered by companies developing connected pen technology as part of their system reporting/output.

Stress and exhaustion among medical students: a prospective longitudinal study on the impact of the assessment period on medical education

BackgroundStress significantly affects both the physical and emotional health of individuals, particularly students in health-related fields. Medical students in Brazil face unique challenges due to the demanding nature of their studies, especially during assessment periods, which heighten academic pressure. These pressures often lead to poor coping strategies and mental health concerns. It is crucial to understand the complex dynamics of stress within medical education to develop strategies that improve student well-being and promote a healthier academic environment. This study aims to investigate the intricate relationship between assessment periods and stress levels among medical students. It seeks to understand how academic demands and sociodemographic factors contribute to stress dynamics during these periods.MethodsAn online observational, longitudinal, and prospective study was conducted from February to October 2022. Medical students were recruited through snowball sampling and participated in surveys administered via Google Forms at two timepoints: before (T1) and during (T2) assessment periods. The surveys collected sociodemographic data and stress symptoms using Lipp’s Inventory of Stress Symptoms for Adults (LSSI).ResultsThe transition from T1 to T2 was defined by a rise in the prevalence of stress from 59.6 to 84.2% (p = 0.001) and a decline in symptom-free students from 40.4 to 15.8% (p = 0.001). There was a significant increase in exhaustion, from 12.3 to 31.6% (p = 0.0001). Higher stress levels were notably more prevalent among younger students (≤ 24 years), females, those from wealthier families, students without scholarships, those without prior degrees, and those in the clinical phase of their studies. However, non significant correlations were found between these sociodemographic and academic factors and the increase in stress.ConclusionThe findings highlight significant concerns regarding the mental health of medical students during assessment periods, marked by increased stress and exhaustion levels. These results emphasize the need for proactive interventions to manage stress effectively in medical education, considering its profound impact on students’ well-being.

Asymmetric Return Connectedness Among Indian Equity Sectors: Insights from Recent Global Disruptions

This article aims to study asymmetric shock transmission among India’s National Stock Exchange sectoral indexes before and amid the COVID-19 crisis and the Russian–Ukraine feud using an asymmetric time-varying parameter vector autoregressive connectedness technique. The daily closing price of equity sector indexes from 1 January 2018 to 31 March 2023 were used. The research reveals strong sectoral return interconnectedness, with negative returns spillover dominating the assessment period. COVID-19 substantially impacted connectedness more than the Russian–Ukraine feud. The sectors such as bank, private bank and financial services were net transmitters of risk, and information technology was the net recipient of risk throughout the assessment period, indicating these sectors are not much affected by these crises. Sector return spillover patterns were similar during the epidemic and the Russian–Ukraine dispute, except for the oil and gas and metal sectors, which shifted roles. These findings suggest that policymakers must recognize and assess the peculiarities of industries that are high-risk transmitters when formulating strategies to prevent market failure or mitigate risk transmission to others. Investors may benefit from recognizing industries that operate as risk transmitters and receivers to create effective risk-mitigation investment strategies amid turbulent times.

A collagen biostimulator improves photoaging pigmentation

AbstractPhotoaging pigmentation conditions such as senile lentigo and melasma show epidermal melanogenic activity and dermal abnormalities, including collagen degradation. A dermal rejuvenation strategy with skin‐lightening therapy directly acting on melanocytes is suggested for photoaging pigmentation. This study investigates whether collagen biostimulation can result in skin lightening of photoaging skin. A split‐face clinical trial was conducted, involving 40 subjects with facial melasma and senile lentigo. Subjects received a poly‐DL‐lactic acid (PDLLA) treatment on one side of their face, whereas the contralateral side received a treatment of normal saline as a control. Assessments were scheduled every month after completing treatments for up to 3 months. Pigmentation was evaluated using the L* value as measured with a chromameter and by investigator global assessment scores (IGA). Subjects reported different outcomes in terms of overall skin quality, including pigmentation, wrinkles and elasticity. Skin biopsies were obtained before the treatment and 4 weeks after completing the treatment. Fontana‐Masson, Masson‐Trichrome and Verhoeff‐van Gieson staining, and fibroblast‐specific protein 1 (FSP1) immunostaining were conducted. The PDLLA treatment demonstrated significant improvements in the L* values and IGA scores from 8 weeks after the subject completed their treatments. These improvements were sustained over a 12‐week assessment period. The subjects reported substantial reductions in both pigmentation and wrinkle severity and elasticity throughout the assessment period. Fontana‐Masson staining showed a marked decrease in pigmentation upon a PDLLA injection compared to the baseline values. Increased immunogenicity of FSP1 and increases in collagen and elastic fibre staining were observed. This study demonstrated remarkable improvements in photoaging pigmentation along with collagen production with a collagen biostimulator. Thus, collagen biostimulators represent a promising therapeutic approach for addressing photoaging signs associated with melasma and senile lentigo. (ClinicalTrials.gov Identifier: NCT05913102).

Durable complete response and overall survival in patients with heavily pretreated, poor-prognosis non-Hodgkin lymphoma to immunoactivating AVM0703 with few and mild drug-related adverse effects.

7077 Background: In 2022, the majority of new cancer drugs in clinical development are aimed at targets that are already saturated with approved drugs1. This is of concern to patients, payers, sponsor/investors, and regulatory agencies. AVM0703 activates a unique immune response mobilizing an endogenous gamma delta TCR+ and invariant TCR+ bispecific Natural Killer T-like cell (γδTCR+iTCR+NKT) (PCT/US21/19773), that has demonstrated clinical anti-cancer activity against a variety of solid and blood cancers. The potential for AVM0703 to fill a gap in the “no-option” R/R NHL treatment landscape led to the launch of the AVM0703-001 clinical trial (The OPAL Study, NCT04329728). 1) Fougner C et al. Herding in the drug development pipeline. Nat Rev Drug Discov. 2023 Aug;22(8):617-618. Methods: An open-label phase 1 trial evaluating the safety and preliminary efficacy of AVM0703 was completed in patients with hematological malignancies. AVM0703 was administered as a single intravenous (IV) infusion to patients enrolled into a 3+3 dose escalation design. Consolidation therapy of investigator’s choice was allowed, preferably 28 days after AVM0703. For each cohort, 3-6 patients were treated, and dose escalation permitted only after the cohort completed a 7-day dose limiting toxicity (DLT) assessment period with no more than 1 DLT. Patients ≥12 years and &gt;40 kg diagnosed with WHO classified lymphoid neoplasms with R/R disease ineligible for transplant or CAR-T were included. The database has not been formally locked and a cutoff date of Dec 13, 2023, is used for presentation of these Phase 1 results. Results: In summary, 17 patients, 39-86 years of age (median 64) with a median of 4 prior lines (range: 1 to 10) received AVM0703 at 6, 9, 12, 18 and 21 mg/kg. Fifteen (88%) were poor prognosis and 4 had CNS involvement. Only 13 of 17 (76.5%) experienced study-drug related adverse events (AEs) during the DLT period; 15 AEs were grade 1 (78.9%), 2 were grade 2 (10.5%), and 2 were grade 3 (10.5%). The most common AEs were insomnia (N=5), hyperglycemia (N=3), and pruritis (N=2). The total number of All-grade TEAEs recorded in 17 patients was 114 within 30 days post dose, with 98.2% of grades 1-3. Median overall survival (OS) in all dose cohorts was 13.3 months, with 8 of 17 patients alive as of 13 Dec 2023. The recommended Phase 2 dose (RP2D) was determined as 18 mg/kg. For the 18 mg/kg group (N=6), long term durable responses were obtained in 66% (3 CR, 1 PR) with an additional patient converting to late CR, nine months survival was 100%, and median OS has not been reached with follow up between 15.9 and 27.8 months (83% still alive). No safety signals have been identified. Conclusions: RP2D AVM0703, with consolidation therapy at day 28 median (range 7 to 240 days) showed no concerning safety signals and promising long-term survival. Clinical trial information: NCT04329728 .

A phase I/II study of maplirpacept in combination with pegylated liposomal doxorubicin (PLD) in patients with platinum-resistant ovarian cancer (OC): Phase 1 results.

e17546 Background: CD47, an overexpressed factor correlated with poor clinical characteristics and prognosis in OC, is an innate immune checkpoint that binds signal regulatory protein alpha (SIRPα) and delivers a signal to suppress macrophage phagocytosis. Maplirpacept (PF-07901801) is a fusion protein consisting of the CD47-binding domain of human SIRPα linked to the Fc region of human IgG4, enhancing phagocytosis by blocking CD47. Blockade of CD47, both alone and combined with doxorubicin, has shown anti-tumor activity in vitro and in vivo in xenograft animal models. PLD 40mg/m2 conveyed poor efficacy (PFS 4 months; ORR 8%), as did bevacizumab + PLD (PFS 5 months; ORR 14%) (AURELIA), highlighting the need for new treatments for platinum-resistant OC. C4971002 [NCT05261490] is an open label, multicenter dose-escalation and expansion study evaluating the safety, preliminary anti-tumor activity, pharmacokinetics and -dynamics of maplirpacept in combination with PLD in patients with platinum-resistant recurrent OC. Methods: The study included adults with platinum-resistant recurrent epithelial OC (PD ≤6 months after platinum-based therapy or unable/unwilling to receive platinum-based therapy). PLD while platinum-resistant or directly prior to study was not permitted. Patients received maplirpacept (12mg/kg Dose Level [DL] 1; 24mg/kg DL2; 48mg/kg DL3) weekly in Cycle 1 and every 2 weeks in Cycle 2+, and PLD (40mg/m2) on Day 1 of each 4-week cycle. Assessments of adverse events (AEs) were based on CTCAE v5.0. Response assessments (RECIST v1.1) were performed every 8 weeks. Results of the Phase I portion, aiming to evaluate the DLTs, the MTD and the RP2D, are presented as of 18 December 2023, after all patients completed the 28-day DLT assessment period. Results: 10 patients were treated (DL1 n=3; DL2 n=3; DL3 n=4) with a median (min, max) age of 69 (53, 77) years, 80% ECOG 1, 60% serous adenocarcinoma. Median (min, max) treatment duration was 14 (8, 32) weeks. Most common adverse events are shown in the table. No DLTs occurred in the assessment period. 1 serious AE (gait disturbance &amp; muscle weakness) related to maplirpacept was reported (DL3). 2 deaths occurred &gt;120 days after 1st dose, both due to disease. 5 (50%) patients had a best response of stable disease, 2 of which were treated into at least Cycle 6. Conclusions: Despite immature anti-tumor activity, maplirpacept + PLD was tolerable at all dose levels, not reaching the MTD. The encouragingly tolerable dose of 48mg/kg thus represents the RP2D which could support further development for this population. Clinical trial information: NCT05261490 . [Table: see text]

Feasibility of implementing whole genome sequencing into routine oncology care.

e15181 Background: The promise of precision oncology to deliver improved patient outcomes is dependent on the availability and appropriate interpretation of individual patient tumor sequencing results. While routine use and clinical utility for comprehensive genomic profiling (CGP) is growing, there are limited data in the U.S. to support the use of whole genome sequencing (WGS) outside of limited specific indications (i.e. acute myeloid leukemia, pediatric, sarcoma). This study highlights reports on the feasibility from a pilot project offering paired germline/somatic WGS to a cohort of oncology patients at an academic medical center. Methods: Eligible patients included those with an active cancer diagnosis, available tumor, and a treating provider within Weill Cornell. There were no specific restrictions. Providers selected patients with newly diagnosed metastatic cancers, rare tumors, refractory tumors, and/or those with uninformative germline testing for hereditary cancer. Reportable germline findings were pathogenic or likely pathogenic (P/LP) variants in known cancer predisposition genes and/or genes on the American College of Medical Genetics list of reportable secondary findings. Clinical actionability of somatic results was determined using the cBioPortal Database and Oncology Knowledgebase. Ordering providers disclosed results to patients. Barriers to enrollment were explored and addressed. Results: Between January 2021 and December 2023, 82 patients had germline/somatic WGS. The most common tumors included breast (17%), prostate (11%), renal (10%), lung (7%), bladder (7%), and colon (5%), with 48% of the cohort represented by rare tumors. Six cases (7.3%) had insufficient quantity/quality. WGS detected single nucleotide variants in 84% (n = 69) of cases, with 39% (n = 27) of those having clinical actionability in the patient’s tumor. Additional somatic results included copy number variants in 83% (n = 68) and transcriptome variants in 17% (n = 14). P/LP germline variants were found in 17% (n = 14) of cases. Barriers to enrollment included: difficulty identifying which patients would benefit most from WGS, lengthy in-person consent process, limited access to pretest genetic counseling, and difficulty procuring and processing tissue specimens. Availability of reflexive in-house CGP since August 2022 also resulted in decreased uptake of this service. Several interventions were implemented to address the barriers, resulting in an increase in enrollment. Conclusions: Paired germline/somatic WGS identified clinically relevant variants for patients with diverse tumors. Results were used to direct treatment decisions and determine eligibility for clinical trials as well as inform hereditary cancer predisposition. An assessment period after WGS implementation is needed to improve workflow. Further research aims to determine optimal accessibility and utilization of WGS for oncologic patients.

Advancements and 4E + Q performance analyses in solar drying for maize kernels preservation: A comprehensive review

AbstractThe world's population is projected to increase, impacting a 60% rise in food production demand by 2050, including the demand for maize. Currently, maize production is estimated to reach 1510 million tons in 2023, necessitating suitable methods for preserving maize kernels to maintain quality and reduce post‐harvest agricultural losses. Although drying methods present a viable solution to address this issue, the majority of farmers in Indonesia still use conventional drying methods, such as open sun drying, which has several drawbacks. Hence, solar drying systems aim to overcome these limitations by harnessing renewable, clean, sustainable, and eco‐friendly energy to support the sustainable development goals (SDGs). This research comprehensively reviews the progress of solar drying technology, providing insights into its working principles, innovative designs, and operational modes across various types of solar dryers. The 4E + Q analysis provides information regarding the performance of solar drying systems, including energy analysis to determine the quantity of energy utilized and exergy analysis to demonstrate irreversibility in thermodynamic processes. Additionally, this analysis highlights environmental impacts such as CO2 emissions and mitigation efforts, while considering economic aspects through lifecycle assessment and payback period methods. The quality assessment of dried maize kernels according to the standards set by the Indonesian National Standard (SNI) is conducted, including proximate analysis, aflatoxin levels, color measurements, and internal cracking analysis.Practical applicationsDrying technology is essential for the food preservation process, enabling the maintenance of product quality and extending storage life by reducing the moisture content to eliminate the activities of microbial agents. The application of solar drying technology harnesses solar radiation as the primary energy source, making it well‐suited for crops like paddy, maize, cassava, etc. The development of solar dryers continues through modifications and the addition of auxiliary systems to achieve more efficient, economical, and sustainable technologies. The hope is that in the future, these technologies can be adopted by farmers on an industrial scale due to low operational costs, ease of operation, and controllable operating conditions. The methodological approach is necessary to evaluate the performance of solar dryers and the quality of dried products through a 4E + Q analysis, it provides information on energy consumption, exergy flow, economic considerations, environmental aspects, and quality assessments against national quality standards (SNI).

Assessment Tool by UNICEF and LATCH Scoring System for Identification of Inadequacy of Breastfeeding in Early Neonatal Period: An Observational Cross-sectional Comparative Study

Background: Breast milk is the most ideal nourishment for a neonate with a high level of bio-efficacy. Learning the right breastfeeding technique is a challenging job, especially for new and young mothers; hence, there is a need for a valid and reliable measuring tool to determine the adequacy of breastfeeding. Objective: To check the adequacy of breastfeeding in mother–neonate dyads using breastfeeding assessment tools by comparing UNICEF and LATCH scoring systems and to test the reliability of the tools through test–retest reliability. Design: An observational cross-sectional comparative study. Setting: Department of Neonatology, Fortis Escorts Hospital, Jaipur, Rajasthan, India. Methods: All stable neonates of ≥34 weeks gestational age born at the private tertiary care hospital were included in the study. Dyads in which breastfeeding was initiated within 6 hours of life were assessed using both LATCH and UNICEF tools on days 1 and 2 of life in the case of normal vaginal delivery and on days 1, 2 and 3 in caesarean deliveries, and were further followed up on days 5 and 7. Results: The median LATCH score and UNICEF score for breastfeeding showed an increase throughout the assessment period. A moderately positive correlation (Spearman’s rho = 0.732) was noticed between the two scores on day 1 of the assessment. On day 2 (Spearman’s rho = 0.81) and day 3 (Spearman’s rho = 0.735), a high positive correlation between the two tools was observed. However, day 4 revealed a low positive correlation (Spearman’s rho = 0.456). Meanwhile, the follow-up scores of both tools showed a high positive correlation (Spearman’s rho = 0.713). Conclusion: The study evidenced a positive correlation between the LATCH and UNICEF scores; both scoring systems displayed a good percent agreement on all the five assessment days. The test–retest reliability was high between the tools on days 1 and 2.

#2251 Long-term systolic blood pressure variability as an independent risk factor for cardiovascular events in kidney transplant recipients

Abstract Background and Aims Cardiovascular (CV) events represent the main cause of death in patients undergoing renal transplantation. Several studies have described the role of blood pressure variability (BPV) in predicting all-cause mortality and fatal and non-fatal CV events in the general population and in diabetic patients. Systolic blood pressure variability (SBPV) has recently been proposed as a predictor of clinical outcomes in patients with chronic kidney disease. However, evidence is still scarce about the prognostic role of BPV in the setting of renal transplantation. The aim of the study was to evaluate the role of long-term SBPV in the development of fatal and non-fatal CV events (myocardial infarction, unstable angina or revascularization, stroke and hospitalization for heart failure) in subjects undergoing kidney transplantation. Method We performed a single-center retrospective observational analysis in a cohort of 272 kidney transplant patients (mean age 64 ± 13 years, 66% men), with a transplant duration ≥12 months and with at least 6 blood pressure measurements at defined intervals (3 months ±15 days) over an assessment period of 18 months. BPV was expressed as standard deviation of ambulatory systolic blood pressure (SBP) and patients were accordingly classified in tertiles (low &amp;lt;9.3 mmHg, medium 9.3-13 mmHg, high &amp;gt;13 mmHg). The role of SBPV was analyzed by Kaplan-Meier (logrank) and its independent effect by Cox Regression. Results Over a mean follow-up of 58.7 ± 17.2 months, 27 subjects (9.9%) developed CV events. For each increase of 2.7 mmHg in SBP standard deviation, the risk for fatal or non-fatal CV events increased almost 3-folds (P = 0.02) and patients in the highest tertile of SBP standard deviation showed a 4-fold increased risk (P = 0.01) (Fig. 1). This relationship was maintained even after incremental adjustment for time-averaged pulse pressure, age, diabetes, prior CV event, and dialysis vintage (HR 3.2, 95% CI 1.1–10.0, p 0.04) (Table 1). Conclusion Long-term BPV represents an independent risk factor for CV events in kidney transplant patients. It is therefore essential to seek for stable long-term blood pressure levels in this population in order to minimize the residual CV risk.

#536 Dedicated patient optimization program delivers effective complex intervention improving the lives of vulnerable HD patients

Abstract Background and Aims Hemodialysis (HD) delivery is failing many patients due to a of lack of available evidence/dialysis-based interventions (previously only studied as single interventions in isolation) to improve outcomes; and the industrialization of institutional-based HD imposing a ‘one size fits all’ approach. To respond to the needs of the most vulnerable patients we have instituted a patient optimization program (POP) to support our Renal Program, fully leveraging our research level assessment tools to provide an individualized appreciation of challenges before delivering an equally individualized complex intervention. The aim was to improve subjective experience [symptoms/health related quality of life (HRQoL) measures] and objective evidence of HD related harm. Method Patients who had suboptimal tolerability to HD were identified and referred by the clinical team (after best efforts to address concern as part of standard care). To understand the patients’ individual challenges, a series of physiological, hemodynamic, and HRQoL assessments were completed. Based on these findings, a series of complex foundational (common to all patients treated) and patient specific interventions were applied, and impact rigorously evaluated. HRQoL/symptoms were measured using the dynamic patient reported outcome measurement tool LEVIL [2-4 weeks leading up to the program (baseline) and continually thereafter]. Comprehensive physiological assessment period was two weeks in length (six HD treatments) and included continuous beat to beat hemodynamic monitoring, intradialytic echocardiography (assess myocardial stunning) and objective volume assessment using ultrasound and bioimpedance. The first session was delivered mirroring routine prescription (establish primary response), subsequent treatments were delivered implementing a variety of foundational, patient/disease specific interventions in a staged manner. Results To date 13 patients have completed the program, referred for a variety of reasons [refractory hypotension (5/13), intradialytic hypotension (2/13) and poor HRQoL [symptoms—cramping, headache, pruritus, insomnia (8/13)]. Complexes of challenges were present in 9/13. All patients had multiple components of dialysis altered. POP was associated with a marked improvement in a range of subjective and objective outcomes. Subjectively, HRQoL improved by 10% [composite LEVIL scores 69.5 ± 15.5 at baseline, 76.5 ± 17 after POP participation (p 0.03)], energy by 18% (64.7 ± 16.2, 76.5 ± 6.4, p 0.01), general wellbeing by 11% (76.5 ± 6.6, 85.2 ± 4.2, p 0.02), and post-dialysis recovery improved from 13.3 ± 16.1 hours to only 2 ± 1.9 hours (p 0.02). Objectively, intradialytic weight gain decreased by 36% (2333.3 ± 1151.8 ml at baseline to 1483.3 ± 591.3 ml, p 0.03), systolic blood pressure improved by 12% [94.9 ± 28.5 mmHg at baseline to 106.2 ± 30 mmHg post optimization p &amp;lt; 0.0001 (despite midodrine being discontinued in 8/13 patients previously dependent on it)]. Tolerability of HD improved (cardiac output 6.4 ± 0.1, 6.5 ± 1, p 0.002 and intradialytic systemic vascular resistance response 15 ± 23.6% at baseline to 48.7 ± 53%, p &amp;lt; 0.0001). Improvement in hemodynamic tolerability led to a reduction in HD induced myocardial stunning larger than reported with any previously applied single intervention; regional wall motion abnormality fell from 5.6 ± 2.4 at baseline (severe stunning) to only 1.2 ± 1.3 (p 0.02) over the two-week program. 2/13 patients who had previously been declined transplantation were accepted and need to repatriate from satellite facilities to in-centre was avoided. Conclusion For the first time, we have created an opportunity for the most challenging patients who have failed conventional best efforts. We have successfully demonstrated the impact of delivering a complex intervention (with a degree of treatment personalization) targeting physiological failure in the most vulnerable HD patients. POP improved HRQoL (principal impact measure), hemodynamic stability and treatment tolerability. Having demonstrated the effectiveness of this approach, we now focus on solutions to up-scale this success.

Effectiveness assessment of protected areas based on the states, trends, and relative changes in forest ecosystem: a case study in the Three Parallel Rivers Region, China

Establishing protected areas (PAs) is a major measure of biodiversity conservation, and various methods have been explored to assess PAs’ effectiveness. However, those methods mainly compared the relative changes in land cover between treated samples inside the PAs and their matched samples outside the PAs, which would produce misjudgments, especially in some climax communities with a relatively steady state. Thus, in this study, we constructed an integrated framework through a series of assessments according to the state, trend, and relative change of each PA to explore the conservation effectiveness of PAs in the Three Parallel Rivers Region in China from 2000 to 2020. Here, “state” refers to the difference among samples from within and outside the PA, assessed through yearly sample mean comparison. “Trend” means linear regression of mean forest area of each PA throughout the assessment period. “Relative change” means the difference in the mean value of the slope of forest changes between the treated samples inside each PA and their matched control samples outside of PAs. The entire forest area within all PAs in the Three Parallel Rivers Region showed a significant increasing trend from 2000 to 2020 (R2 = 0.919, P&amp;lt;0.05). Among all the PAs, twelve (86%) had a positive effect on protecting the forest ecosystem, and two had a nonsignificant effect. Among the factors affecting the state and relative change in PAs’ forests, the annual total precipitation was the most important, followed by distance to the nearest road. Moreover, the management-level variable was an essential factor in the state of PAs’ forest ecosystems, which indicated that national PAs (nature reserves and natural parks) were in a better state than local (provincial- and county-level) nature reserves. Overall, the conservation effectiveness of forests in PAs was assessed at a regional scale in the Three Parallel Rivers Region, implying that our framework would be additional useful in regions with high biodiversity and steady ecosystems. This framework better avoids underestimating conservation effectiveness assessment tasks than traditional methods do. Thus, we posit that this framework is suitable for future global or country-level assessments.

Comparing the life cycle costs of a traditional and a smart HVAC control system for Australian office buildings

Many smart technologies have been introduced in buildings with the aim to reduce the energy and GHG emissions associated with their operation, particularly through improved control systems for regulating heating, ventilation and air conditioning (HVAC) equipment. Despite their energy saving potential, only a few studies have comprehensively assessed the costs associated with their practical implementation from a life cycle perspective. Accordingly, this study quantifies and compares the life cycle costs of a smart HVAC control system with that of a traditional control system, in the context of an Australian office building. For both systems, the required hardware are specified based on the characteristics of these systems and the layout of the serviced spaces in the reference building. The costs incurred over the period of assessment are quantified using the net present cost (NPC) approach. To evaluate the effects of these control systems on the operational energy costs of the building HVAC system, the control logics of both these systems are modelled through building energy simulations. The results show that, over the period of assessment, the smart control system incurred a higher total cost compared to the traditional control system. However, the findings from the simulations show that the HVAC energy cost savings achieved through the specification of the smart control system offset the additional cost incurred to deploy this system over the traditional control system. The smart control system resulted in HVAC operational cost savings between 9 % and 10 % compared to the traditional control system. Sensitivity analyses indicated that the total life cycle costs varied between −27 % and +50 %, with the discount rate and energy price increase rate being the most influential parameters.

The association of body mass index variability with cardiovascular disease and mortality: a mediation analysis of pooled cohorts.

We aimed to investigate the effect of BMI variability on CVD and mortality and to explore the mediation effects of the main cardiovascular risk factors contributing to this association. Participants aged 40-65 years were pooled from three cohort studies(ARIC [Atherosclerosis Risk in Communities], MESA [Multi-ethnic Study of Atherosclerosis], and TLGS [Tehran Lipid and Glucose Study]. We employed root mean squared error of the fractional mixed model to calculate BMI variability in the measurement period. In the event assessment period, the hazard ratios for CVD and mortality were estimated using Cox proportional hazard regression models. In the next step, the mediation and interaction effects of fasting plasma glucose, total cholesterol, and systolic blood pressure were determined. A total of 19073 participants were included in this pooled analysis. During a median of 20.7 years of follow-up, 3900 (20.44%) CVD and 6480 (33.97%) all-cause mortality events were recorded. After adjusting for potential confounders, BMI variability was linked to the 1.3 (1.2-1.4) and 1.7 (1.6-1.8) increased risk of CVD and mortality, respectively. Fasting plasma glucose mediated approximately 24% and 8% of the effect of BMI variability on CVD and mortality, respectively. However, systolic blood pressure and total cholesterol did not have mediation effects in this association. High BMI variability is independently associated with the development of CVD and mortality. This association is partly mediated through fasting plasma glucose. Modern cardiometabolic therapies that lower fasting glucose may reduce the risk of future CVD and mortality in individuals with high BMI variability.

Interpreting Change in Disorders of Consciousness Using the Coma Recovery Scale-Revised.

The purpose of this study was to differentiate clinically meaningful improvement or deterioration from normal fluctuations in patients with disorders of consciousness (DoC) following severe brain injury. We computed indices of responsiveness for the Coma Recovery Scale-Revised (CRS-R) using data from a clinical trial of 180 participants with DoC. We used CRS-R scores from baseline (enrollment in a clinical trial) and a 4-week follow-up assessment period for these calculations. To improve precision, we transformed ordinal CRS-R total scores (0-23 points) to equal-interval measures on a 0-100 unit scale using Rasch Measurement theory. Using the 0-100 unit total Rasch measures, we calculated distribution-based 0.5 standard deviation (SD) minimal clinically important difference, minimal detectable change using 95% confidence intervals, and conditional minimal detectable change using 95% confidence intervals. The distribution-based minimal clinically important difference evaluates group-level changes, whereas the minimal detectable change values evaluate individual-level changes. The minimal clinically important difference and minimal detectable change are derived using the overall variability across total measures at baseline and 4 weeks. The conditional minimal detectable change is generated for each possible pair of CRS-R Rasch person measures and accounts for variation in standard error across the scale. We applied these indices to determine the proportions of participants who made a change beyond measurement error within each of the two subgroups, based on treatment arm (amantadine hydrochloride or placebo) or categorization of baseline Rasch person measure to states of consciousness (i.e., unresponsive wakefulness syndrome and minimally conscious state). We compared the proportion of participants in each treatment arm who made a change according to the minimal detectable change and determined whether they also changed to another state of consciousness. CRS-R indices of responsiveness (using the 0-100 transformed scale) were as follows: 0.5SD minimal clinically important difference = 9 units, minimal detectable change = 11 units, and the conditional minimal detectable change ranged from 11 to 42 units. For the amantadine and placebo groups, 70% and 58% of participants showed change beyond measurement error using the minimal detectable change, respectively. For the unresponsive wakefulness syndrome and minimally conscious state groups, 54% and 69% of participants changed beyond measurement error using the minimal detectable change, respectively. Among 115 participants (64% of the total sample) who made a change beyond measurement error, 29 participants (25%) did not change state of consciousness. CRS-R indices of responsiveness can support clinicians and researchers in discerning when behavioral changes in patients with DoC exceed measurement error. Notably, the minimal detectable change can support the detection of patients who make a "true" change within or across states of consciousness. Our findings highlight that the continued use of ordinal scores may result in incorrect inferences about the degree and relevance of a change score.

Assessment of land use and land cover change detection and prediction using deep learning techniques for the southwestern coastal region, Goa, India.

Understanding the connections between human activities and the natural environment depends heavily on information about land use and land cover (LULC) in the form of accurate LULC maps. Environmental monitoring using deep learning (DL) is rapidly growing to preserve a sustainable environment in the long term. For establishing effective policies, regulations, and implementation, DL can be a valuable tool for assessing environmental conditions and natural resources that will positively impact the ecosystem. This paper presents the assessment of land use and land cover change detection (LULCCD) and prediction using DL techniques for the southwestern coastal region, Goa, also known as the tourist destination of India. It consists of three components: (i) change detection (CD), (ii) quantification of LULC changes, and (iii) prediction. A new CD assessment framework, Spatio-Temporal Encoder-Decoder Self Attention Network (STEDSAN), is proposed for the LULCCD process. A dual branch encoder-decoder network is constructed using strided convolution with downsampling for the encoder and transpose convolution with upsampling for the decoder to assess the bitemporal images spatially. The self-attention (SA) mechanism captures the complex global spatial-temporal (ST) interactions between individual pixels over space-time to produce more distinct features. Each branch accepts the LULC map of 2 years as one of its inputs to determine binary and multiclass changes among the bitemporal images. The STEDSAN model determines the patterns, trends, and conversion from one LULC type to another for the assessment period from 2005 to 2018. The binary change maps were also compared with the existing state of the art (SOTA) CD methods, with STEDSAN having an overall accuracy of 94.93%. The prediction was made using an recurrent neural network (RNN) known as long short term memory network (LSTM) for the year 2025. Experiments were conducted to determine area-wise changes in several LULC classes, such as built-up (BU), crops (kharif crop (KC), rabi crop (RC), zaid crop (ZC), double/triple (D/T C)), current fallow (CF), plantation (PL), forests (evergreen forest (EF), deciduous forest (DF), degraded/scurb forest (D/SF) ), littoral swamp (LS), grassland (GL), wasteland (WL), waterbodies max (Wmx), and waterbodies min (Wmn). As per the analysis, over the period of 13 years, there has been a net increase in the amount of BU (1.25%), RC (1.17%), and D/TC( 2.42%) and a net decrease in DF (3.29%) and WL(1.44%) being the most dominant classes being changed. These findings will offer a thorough description of identifying trends in coastal areas that may incorporate methodological hints for future studies. This study will also promote handling the spatial and temporal complexity of remotely sensed data employed in categorizing the coastal LULC of a heterogeneous landscape.

Strengthening the agricultural entrepreneurship: Insights on transformative influence

Agri-entrepreneurship being very important component of attracting youth to agriculture, the efforts made by different public agencies in India in this direction through various interventions and enterprises needed to be studied. Mushroom (Agaricus bisporus) production is one of the most popular enterprises promoted to pursue this objective throughout India. This study considered 2016–17 as the base year and 2020–21 as the assessment year. Mushroom production in India almost doubled during the assessment period (1.29 lakh tonnes in 2016–17 and 2.59 lakh tonnes in 2020–21) at a robust compound annual growth rate of 19.17%. The net agricultural income of the respondents at national level (other than mushroom income) was ₹1.25 lakh/annum during 2020–21 while their net income from mushroom cultivation was 2.48 lakh/annum. On an average 532 man-days of employment per unit was generated by the mushroom entrepreneurs at national level with considerable variation in income and employment generation across the states/UTs. Age of the entrepreneur was found having negative effect on employment generation, validating the relevance of attracting rural youth to agriculture in India. The lack of ability of resource centres for building capacity of the entrepreneurs for generating net income to the level of sizeable proportion of their annual expected livelihood was observed to be the strong reason for higher attrition rate in this enterprise. The insights suggest that redesigning of capacity building programs and institutional supports as per the current challenges in entrepreneurship development can better influence the ultimate outcomes.

Thermal efficiency and performance analysis of 50 MW concentrated solar power plant

This study evaluates the operational efficiency and performance of the Shagaya 50 MW Concentrated Solar Power (CSP) plant in Kuwait that has been operational since February 2019. Utilizing Parabolic Trough technology, the plant incorporates a large Solar Field (SF) comprising 8 platforms with total of 206 solar-collector loops. Thermal energy captured by the SF is utilized in a Low Temperature Rankine Cycle to generate electricity via water-steam cycle and heat exchangers, with a nominal turbine capacity of 50 MW. Supported by a thermal energy storage (TES) system capable of storing 1200 MWht energy in molten salt. Through a comprehensive assessment spanning 41 months, real-time operational data is analysed to evaluate the CSP-TES system's efficacy within Kuwait's climatic conditions. Various performance parameters are examined, providing insights into CSP technology's practical implications and operational strategies. Driven by the annual difference in downtime and TES availability, comparative analysis of the plant's annual electricity production over the three years reveals notable variations: 74.99 GWh in 2019, 160.62 GWh in 2020, and 140.04 GWh in 2021, corresponding to capacity factors of 19 %, 40.75 %, and 35.53 %, respectively. The findings underscore the strong correlation between the SF and TES system in determining overall plant efficiency. The study also highlights the impact of high wind speeds on plant operation, triggering shutdowns on 9 days during the assessment period. Additionally, soiling losses in the SF are assessed through daily reflectivity measurements, guiding cleaning efforts using semi-automated armed trucks. Seasonal peaks in cleanliness factor coincide with local spring season, underlining the detrimental effect of reflectivity losses on plant output due to higher dust mass densities. A design flaw causing frequent breakdowns of receiver tubes under high winds is identified and addressed.