Frequent Interval Research Articles

Stable isotope hydrology of a polymictic lake: Capturing transience of groundwater interactions

Although there have been many studies of groundwater inflow to small lakes, no systematic attention has been paid to the role of the time interval in the reliability of transient flow analysis. We addressed this issue in a two-year study of the isotope hydrology and water budget of a small lake in eastern Washington State (USA) that has been subject to limited management over several decades. The weighted local meteoric water line is δ2H = 7.14 δ18O – 5.22, reflecting the impact of convective recycling in this semi-arid region of inland northwestern North America. Groundwater inflow to the lake was quantified over two years using a short-interval isotopic transient mass balance approach. Calculated inflow was less than a fifth of the lake’s total water budget. Unrealistic temporal fluctuation of the calculated inflow was apparently correlated with fluctuation of the observed isotopic ratio of lake water (δL). We obtained realistic lake fluctuation and groundwater–lake exchange estimates by experimenting with the time interval of the isotope mass balance. It is crucial to acknowledge that each lake possesses unique characteristics that influence hydrologic and isotopic variations. Therefore, the optimal time interval for sampling and calculating mass balance may vary among different small lakes. Our findings have implications for long-term studies with frequent interval sampling.

Automatic Pet Feeder Using Assistant

Nowadays most of us fascinated to have pets at their home. But these pets have to be taken care properly. Their feeding on time is an important task as they become part of our family. But in our busy schedule we fail to pay attention on our pet thus it doesn’t get proper food on time. This paper addresses the above issue by introducing an Automatic Pet Feeding System to ensure feeding pet on frequent interval of time. In our project we used two methods to feed the Pet, one is by Camera and another by using Google Assistant. When the DC servo motor runs, the motor rotates the propeller which is in the feeding device, which drops down pet food through the pipe into perforated feeding bowl. The water pump will be kept in a tank containing water. When the water pump runs, the water is pumped into the water bowl of pet. The user in order to feed their pet have to give a command on their Smart Phones such as “Okay Google”, “Feed my Pet”, with the help of this command the machine will do its following work. The user can also specify the time to feed their pet on schedule using Google Assistant

Mitotic abnormalities precede microsatellite instability in lynch syndrome-associated colorectal tumourigenesis

Lynch syndrome (LS) is one of the most common hereditary cancer syndromes worldwide. Dominantly inherited mutation in one of four DNA mismatch repair genes combined with somatic events leads to mismatch repair deficiency and microsatellite instability (MSI) in tumours. Due to a high lifetime risk of cancer, regular surveillance plays a key role in cancer prevention; yet the observation of frequent interval cancers points to insufficient cancer prevention by colonoscopy-based methods alone. This study aimed to identify precancerous functional changes in colonic mucosa that could facilitate the monitoring and prevention of cancer development in LS. The study material comprised colon biopsy specimens (n=71) collected during colonoscopy examinations from LS carriers (tumour-free, or diagnosed with adenoma, or diagnosed with carcinoma) and a control group, which included sporadic cases without LS or neoplasia. The majority (80%) of LS carriers had an inherited genetic MLH1 mutation. The remaining 20% included MSH2 mutation carriers (13%) and MSH6 mutation carriers (7%). The transcriptomes were first analysed with RNA-sequencing and followed up with Gorilla Ontology analysis and Reactome Knowledgebase and Ingenuity Pathway Analyses to detect functional changes that might be associated with the initiation of the neoplastic process in LS individuals. With pathway and gene ontology analyses combined with measurement of mitotic perimeters from colonic mucosa and tumours, we found an increased tendency to chromosomal instability (CIN), already present in macroscopically normal LS mucosa. Our results suggest that CIN is an earlier aberration than MSI and may be the initial cancer driving aberration, whereas MSI accelerates tumour formation. Furthermore, our results suggest that MLH1 deficiency plays a significant role in the development of CIN. The results validate our previous findings from mice and highlight early mitotic abnormalities as an important contributor and precancerous marker of colorectal tumourigenesis in LS. This work was supported by grants from the Jane and Aatos Erkko Foundation, the Academy of Finland (330606 and 331284), Cancer Foundation Finland sr, and the Sigrid Jusélius Foundation. Open access is funded by Helsinki University Library.

Abstract LB118: HM16390, a novel long-acting IL-2 analog with fine-tuned binding affinities to IL-2 receptor subunits for favorable safety profile, exhibits potent tumor killing effect in the various tumor syngeneic models

Abstract Although recombinant human IL-2 (rhIL-2, aldesleukin) produced approximately a 15% objective response rate in patients with renal cell carcinoma (RCC) and metastatic melanoma, its IL-2Rα (CD25)-biased binding and short half-life (t1/2 in human: 13-85 min) require a high dose and frequent dosing interval, leading to systemic toxicity such as vascular leak syndrome (VLS) and cytokine release syndrome (CRS). To overcome this limitation, various research groups are developing engineered IL-2 muteins with abolished CD25 binding affinity. While such IL-2 muteins may reduce CD25-mediated toxicity, there is a risk of a lopsided immune response. Furthermore, concomitantly reduced affinity to IL-2Rβ (CD122) may cause insufficient anti-tumor activity. We are developing HM16390, a long-acting IL-2 analog with a significantly increased binding affinity to CD122 for potent tumor killing effect. Simultaneously, optimal binding property to CD25 was introduced for a suppression of uncontrolled systemic immune response via peripheral Treg expansion. From these novel sequence modifications, HM16390 exhibited approximately 14-fold potent activity in human NK and CD8+ T cells compared to rhIL-2 and comparable activity with rhIL-2 in human Tregs (EC50 of STAT5 phosphorylation) without undesired release of cytokines associated with CRS. In B16F10 mouse model, HM16390 has a longer-lasting PK property (t1/2: 14.2~26.0 hr) after single subcutaneous (SC) administration. CD8+ T cells were significantly increased in peripheral blood along with a transient increase of peripheral Tregs, suggesting that HM16390 not only has a significant effect on expansion of CD8+ T cells but can simultaneously modulate exaggerated peripheral immune response. It is also noteworthy that, unlike in the peripheral, Tregs were drastically reduced in the tumor immune microenvironment, and CD8+ T cells were significantly increased. Next, in orthotopic model of mouse RCC (RENCA-luc cell implantation), across treatment groups, 40%(n=4/10) to 80%(n=8/10) of animals achieved complete tumor regression in dose-dependent manner after once weekly SC injection of HM16390 for 4 weeks. Furthermore, tumor nodules were not observed in lung and kidney after intravenous (IV) rechallenge of RENCA cells in the mice cured by HM16390 for at least 4 months after drug discontinuation. This indicates a long-term immunological memory response of generated memory cells by treatment of HM16390. In conclusion, HM16390 demonstrates potent and durable anti-tumor activity in various murine tumor models via its enhanced CD122 binding affinity, and incorporated optimal CD25 binding affinity may alleviate systemic toxicity by immunomodulatory role of peripheral Tregs. Citation Format: Sol-Bi Shin, Jinyoung Kim, Jaehyuk Choi, Seongju Jeong, Yunjae Kim, Jooyun Byun, Sungmin Bae, Daejin Kim, In Young Choi. HM16390, a novel long-acting IL-2 analog with fine-tuned binding affinities to IL-2 receptor subunits for favorable safety profile, exhibits potent tumor killing effect in the various tumor syngeneic models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB118.

Retrospective Observational Study on Real-World Bortezomib Prescribing Patterns and Outcomes in Newly Diagnosed Multiple Myeloma

Introduction: Most induction regimens for multiple myeloma (MM) contain bortezomib. In most clinical trials, bortezomib has been prescribed either intravenously or subcutaneously twice per week in 21-day or 28-day cycles. However, several retrospective single-center studies have shown that once-weekly bortezomib has comparable efficacy and less peripheral neuropathy compared to twice-weekly bortezomib ( Sidana et al, PLoS One 2017; Cook et al, AJH 2021). These findings have also been confirmed by a secondary analysis of data from three prospective Phase 3 randomized studies ( Mateos et al, Haematologica 2014). As such, many clinicians have adopted once-weekly bortezomib regimens in routine care in the past decade. However, the real-world (RW) prevalence and efficacy of once-weekly vs twice-weekly bortezomib regimens in a larger population have not yet been characterized. Methods: This study used US nationwide longitudinal Flatiron Health electronic health record-derived de-identified data. We included patients aged 18-70 years with newly diagnosed MM between 2017-2022 with ≥ 6 months of follow-up and ≥ 2 clinical visits who were treated with a first-line (1L) bortezomib-containing regimen. Patients aged >70 were excluded a priori given the likelihood of altered practice patterns and more frequent comorbidities. Twice-weekly bortezomib was defined as patients for whom the most frequent interval between two doses of 1L bortezomib within a cycle was 3.0-4.9 days, while once-weekly bortezomib was defined as a corresponding interval of 5.0-9.9 days. We used multivariable logistic regression to assess demographic and clinical factors associated with once-weekly vs twice-weekly (reference) bortezomib. RW progression free survival (rwPFS) and RW overall survival (rwOS) from 1L treatment initiation were estimated using the Kaplan-Meier method. Outcomes were compared using Cox proportional hazards model including transplant as a time-varying covariate and adjustment for other demographic and clinical factors. Results: Of 2,522 patients included, 927 (36.8%) received twice-weekly while 1,522 (63.2%) received once-weekly bortezomib. Approximately half of patients (50.3%) were non-Latinx White, 21.7% non-Latinx Black, and 8.0% Latinx. Most patients were treated in the community setting (78.8%). Rates of once-weekly bortezomib administration were 66.2% and 62.1% among patients treated at academic and community practices, respectively. The frequency of weekly bortezomib use increased over time, from 58.0% between 2017-2019 to 68.8% between 2020-2022. In multivariate analysis, ECOG PS ≥ 2 (odds ratio [OR] 1.50; [95% CI 1.14 to 1.99] vs ECOG PS 0), and more recent year of diagnosis (OR 1.14; [95% CI 1.08 to 1.20] per year) were associated with higher odds of receiving once-weekly bortezomib. Conversely, Latinx patients vs non-Latinx White (OR 0.60 [95% CI 0.44 to 0.82]) and patients with ≥ 2 high-risk cytogenetic abnormalities (HRCA) vs 0 HRCA (OR 0.66 [95% CI 0.48 to 0.91]) had lower odds of receiving once-weekly bortezomib administration. No significant associations were found between gender, ISS stage, practice setting, insurance category, or baseline creatinine. There was no statistically significant difference in rwPFS among patients receiving once-weekly (median 37.3 months, 95% CI 33.8 to 42.5) vs twice-weekly bortezomib (median 39.2 months, 95% CI 32.9 to 42.8) (HR 0.87 [95% CI 0.77 to 1.00]) (Figure 1A). Similarly, there was no statistically significant difference in rwOS with median 25.5 months follow-up (Figure 1B). Median rwOS was not reached in either group (hazard ratio 0.89 [95% CI 0.75 to 1.07]). Discussion: We evaluated US bortezomib prescribing patterns for the first time in the modern era using a large nationwide RW-study. Whereas prescribing patterns have shifted towards once-weekly bortezomib over time, over 30% of patients diagnosed in the last three years received twice-weekly bortezomib. Importantly, once-weekly and twice-weekly bortezomib performed comparably with regard to rwPFS and rwOS. While our study did not analyze neuropathy or patient quality of life, once-weekly bortezomib is known to be associated with less neuropathy and less time in clinic. These data further support the conclusion that once-weekly bortezomib should be considered the standard of care for newly diagnosed patients with MM.

SAT028 Beneficial Effect On Intestinal Growth Of A Long-Acting GLP-2 Analog, HM15912, After Treatment Switching From Conventional GLP-2 Drug Or Other Long-Acting GLP-2 Analogs Under Clinical Development In Animal Model

Abstract Disclosure: C. Park: Employee; Self; Hanmi Pharm. Co., Ltd. J. Choi: Employee; Self; Hanmi Pharm. Co., Ltd. E. Park: Employee; Self; Hanmi Pharm. Co., Ltd. H. Kwon: Employee; Self; Hanmi Pharm. Co., Ltd. S. Bae: Employee; Self; Hanmi Pharm. Co., Ltd. D. Kim: Employee; Self; Hanmi Pharm. Co., Ltd. Y. Kim: Employee; Self; Hanmi Pharm. Co., Ltd. I. Choi: Employee; Self; Hanmi Pharm. Co., Ltd. The widespread use of teduglutide, which is only approved GLP-2 analog drug for short bowel syndrome (SBS), may be still limited due to insufficient efficacy and leading to a significant burden for patients by daily administration. Hence, several long-acting GLP-2 analog drugs targeting once a week are currently in clinical development. Here, we investigated that HM15912, a novel long-acting GLP-2 analog, enabled to achieve additional small bowel trophic effect after switching from those existing GLP-2 analogs. To investigate additional intestinotrophic efficacy after switching from teduglutide to HM15912, C57BL/6 mice treated with twice daily administration of teduglutide for 2 weeks were switched to once-weekly administration of HM15912, or continued the typical treatment of teduglutide for the remaining 2 weeks. HM15912 treatment significantly increased wet weight of SI (72.9% over vehicle) compared to teduglutide treated group (39.4% over vehicle) after 2 weeks. After 2 more weeks treatment, while showing the maintained the increased SI weight in teduglutide treated group (58.3% at week 3 and 41.1% at week 4 over vehicle), SI weight was further increased after switching to HM15912 (61.2% at week 3 and 68.5% at week 4 over vehicle). Next, we synthesized GLP-2 analogs to have same sequences with glepaglutide and apraglutide. SD rats treated with every other day administration of these long acting GLP-2 analogs for 2 weeks were switched to HM15912 or continued the typical treatment of them for the remaining 2 weeks. HM15912 treatment significantly increased wet weight of SI compared to weekly GLP-2 analog drug treated groups after 2 weeks (84.4% versus 41.5% or 26.6% over vehicle). After 2 more weeks treatment, while showing the slight increment in SI weight in the long-acting GLP-2 analogs (50.5% and 37.4% over vehicle), SI weight was further increased after switching to HM15912 (82.1% and 90.7% over vehicle, respectively). In line with these results, D-xylose absorption capacity was also significantly increased after switching from existing GLP-2 analogs to HM15912. As a results, HM15912 significantly promoted small intestinal growth than existing GLP-2 analogs even with a less frequent dosing interval of once a week in rodents. A phase 2 clinical study of once-monthly dosing in patients with SBS is ongoing to evaluate the clinical relevance of these findings. Presentation: Saturday, June 17, 2023

Healthcare costs, resource utilization, and productivity loss associated with colorectal cancer screening.

To evaluate healthcare costs, resource utilization, associated costs, and lost productivity for colorectal cancer (CRC) screening in an average-risk population. This retrospective cohort study identified average-risk individuals (50-75 years) with claims in the Optum Research Database for CRC screening test between 1 January 2014 to 31 December 2018. Index date was defined as the first date of a claim for colonoscopy, fecal immunochemical test (FIT), guaiac-based fecal occult blood test (FOBT) or multi-target stool DNA test (mt-sDNA). Screening costs were evaluated with descriptive statistics and multivariable analyses, adjusting for patient characteristics and index screening costs. In total, 903,831 individuals were identified by test groups: mt-sDNA (n = 29,614), FIT (n = 254,002), guaiac-based FOBT (n = 112,757) and colonoscopy (n = 507,458). Adjusted costs for index screening were, colonoscopy ($3,029), mt-sDNA ($752), FIT ($45), and (FOBT ($153). Adjusted costs across the six months following the index screening were $146 for colonoscopy, $329 for mt-sDNA, $306 for FIT, and $412 for FOBT. Colonoscopy had the highest costs for lost productivity. Screening colonoscopy had the highest productivity loss and healthcare costs up-front, suggesting potential cost benefits for noninvasive screening modalities. The more frequent screening interval required for FIT and FOBT resulted in a higher yearly cost than colonoscopy or mt-sDNA.

Intratympanic Steroid Use for Sudden Sensorineural Hearing Loss: Current Otolaryngology Practice in the Kingdom of Saudi Arabia

Abstract Objectives: Sudden sensorineural hearing loss (SSNHL) is commonly defined as a hearing loss of more than 30 decibels in three consecutive frequencies that occurs within 72 h. In most cases, it is considered idiopathic, and an evidence-based strategy to treat it is still debated. We aim to analyze the current practice of intratympanic steroid injection (ITSI) for SSNHL in the Kingdom of Saudi Arabia (KSA) and compare it to the published data from the United Kingdom (UK), the United States (US), and continental Europe. Methodology: A survey of 28 questions was distributed among Otolaryngology Consultants and Specialists of KSA. It includes questions about demographics, indications for IT treatment, procedure, follow-up, and outcomes. Results: We received 75 responses. Around 66% of them indicated that they use ITSI to treat idiopathic SSNHL (ISSNHL). Forty-six percent (n = 23) did not use ITSI as a primary therapy. Forty percent (n = 20) used it in combination with other treatments, including oral steroids, and 14% (n = 7) used it as a primary monotherapy. The majority (36%, n = 18) considered using ITSI for up to 1 month. The commonly used course of treatment for our ear, nose, and throat (ENT) doctors was three injections (50% n = 25), with a weekly dose being the most frequent interval (42% n = 21). Conclusion: This study showed wide variability in practice among Saudi ENT clinicians. This variation has been found across countries, in the UK, US, and continental Europe, which tells us that this is a global issue and there is not yet one unified protocol to be followed in the treatment of ISSNHL.

Measurement of Cyclooxygenase Products in Plasma as Markers for Inhibition of Cyclooxygenase Isoforms by Oral Meloxicam in New Zealand White Rabbits (Oryctolagus cuniculus ).

Pain management in rabbits is a challenging task that is complicated by the rabbit's ability to hide signs of distress and the limited pharmacologic data available for this species. Pharmacokinetic data has shown that in rabbits, meloxicam, a nonsteroidal anti-inflammatory NSAID, reaches plasma concentrations that are known to provide analgesia in dogs and cats; these concentrations could theoretically alleviate pain in rabbits. However, the inhibitory effects of meloxicam on cyclooxygenase (COX) isoforms have not been studied in rabbits. In this study, we measured the products of COX-1 and COX-2 after the oral administration of a single 1 mg/kg dose of meloxicam to New Zealand White rabbits (n = 6). Blood samples were collected before drug administration (T0) and then at predetermined time points over 48 h. Plasma prostaglandin E₂ (PGE₂ ) and thromboxane (TxB₂) concentrations were measured as surrogate markers for COX-1 and COX-2, respectively, by using commercial ELISA kits. After meloxicam administration, both TxB₂ and PGE₂ plasma concentrations fell significantly below baseline, with maximal mean reductions to 80% and 60% of baseline at 8 h, respectively. The reduction in PGE₂ concentrations was followed by a significant increase that moved its mean plasma concentrations toward baseline between 8 and 24 h. Adverse effects such as lethargy, inappetence, or changes in fecal production were not observed in any rabbits. In conclusion, meloxicam appeared to significantly inhibit both COX-1 and COX-2 with a time course similar to previously reported meloxicam plasma concentration-time profiles in rabbits. Our data suggest that a dosage of 1 mg/kg given orally could provide analgesia to rabbits, but a more frequent dosing interval than the currently recommended daily dosing may be required to maintain clinical efficacy.

Abstract CT052: A phase 1/2 randomized study of imvotamab monotherapy and in combination with loncastuximab tesirine in relapsed/refractory non-Hodgkin lymphomas

Abstract Background: Recent advances in the treatment of non-Hodgkin lymphoma (NHL) have transformed the landscape and provided significant benefits to patients. Novel agents that target CD19 and CD20 on B cells, such as bispecific T-cell engagers and chimeric antigen receptor T-cell (CAR-T) therapy, have demonstrated benefit for patients in the relapsed and refractory setting. However, these agents can often be associated with significant toxicity and there is a need for new therapies that can provide clinical benefit with a superior safety profile. Imvotamab is a novel CD20 x CD3 bispecific antibody utilizing an IgM backbone. This allows targeting of up to 10 CD20 binding sites for every CD3 site. In preclinical models, imvotamab demonstrated encouraging antitumor activity and stimulated T-cells in a more physiologic manner than IgG-based antibodies, which may reduce adverse events typically associated with T-cell engagers and CAR-T, such as CRS and neurotoxicity. Loncastuximab tesirine is a CD19-targeting antibody-drug conjugate approved by the US FDA and EMA for relapsed DLBCL after 2 lines of systemic therapy. Loncastuximab tesirine has shown activity in both DLBCL and FL. Combining therapies such as loncastuximab tesirine, which targets CD19 and induce apoptosis of cancer cells, with imvotamab’s ability to eliminate CD20+ tumor cells by engagement with T-cells, may improve treatment outcomes among patients with NHL via synergistic mechanisms of action. Methods: This study is a Phase 1/2, multicenter, single-arm clinical trial of imvotamab as monotherapy and in combination with loncastuximab tesirine for patients with relapsed/refractory NHL. Phase 1a Dose Escalation is complete with no DLTs or neurotoxicity AEs up to 1000mg dose titration. Phase 1b Combination will evaluate imvotamab and loncastuximab tesirine in patients with R/R 2nd line or later NHL. Phase 2 monotherapy Dose Selection is currently ongoing. The Phase 2 component randomizes patients at two different dose levels (100 mg and 300 mg plateau dose) in two separate indications (R/R DLBCL and R/R FL). Patients receive weekly dosing on Day 1, 8, and 15 of each 21- day cycle. Dosing begins at 15 mg and is increased weekly for 3-4 weeks to reach the plateau dose. Patients then stay at the plateau dose until disease progression or unacceptable toxicity. Patients who achieve a response by Week 12 may switch to a less frequent dosing interval of every 3 weeks. Primary endpoints include frequency and severity of adverse events and objective response rate (ORR) based on Lugano criteria. Correlative biomarker studies will evaluate the relationship of clinical benefit with blood and tissue biomarkers. The study is currently open with patients enrolling in Phase 2 at time of submission. Phase 1b Combination is expected to begin enrollment in the first quarter of 2023. Clinical trial information: NCT04082936. Citation Format: Catherine Diefenbach, Won Seog Kim, Chan Cheah, Ajay K. Gopal, Philippe Armand, Ian Flinn, Gareth P. Gregory, Sung-Soo Yoon, Loretta Nastoupil, Jennifer Lue, Vincent Ribrag, Javier Briones, Antonio Salar-Silvestre, Anna Sureda-Balari, Matthew Ku, Hans Cruz, Paul Thaler, Ibrahim Qazi, Rachel Wei, Maya Leabman, Genevive Hernandez, Iris Sison, Elizabeth Budde. A phase 1/2 randomized study of imvotamab monotherapy and in combination with loncastuximab tesirine in relapsed/refractory non-Hodgkin lymphomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT052.

An Efficient Task Synthesis Method Based on Subspace Differential Patterns for Arrangements of Event Intervals Mining in the Avionics Cloud System Architecture

Avionics Cloud is a new multi-platform avionics system architecture that provides dynamic access, resource pooling, intelligent scheduling, on-demand service and other cloud computing features. Using Avionics Cloud to rationalize the order of multi-flight platform task execution and realize multitask synthesis is a challenging problem. In this paper, we propose an Efficient Task Synthesis Method based on Subspace Differential Patterns for Arrangements of Event Intervals Mining-DiMining. For tasks executed in a multi-platform Avionics Cloud system with dynamic characteristics of time intervals, DiMining is proposed. The algorithm mines the differential frequent task execution event interval patterns related to execution efficiency from the scenario dataset with high execution efficiency and the scenario dataset with low execution efficiency in order to identify key task patterns related to execution efficiency and improve the task synthesis design efficiency of the multi-platform Avionics Cloud system. Furthermore, in order to improve the mining efficiency of the algorithm, this algorithm designs a variety of pruning strategies to ensure that two differential time interval patterns with high and low functional execution efficiency are mined at one time without preserving the set of candidate items. The experimental results show that the DiMining algorithm is more efficient than the traditional algorithm on the open dataset. The DiMining algorithm is used to mine the 350-field high-efficiency operation scenario dataset and the 350-field efficiency operation scenario dataset under the constructed typical UAV cluster co-detection task scenarios. Based on the simulation results, the DiMining algorithm is able to effectively support the design of multi-platform Avionics Cloud system task synthesis architecture and improve the efficiency of UAV cluster collaborative detection.

Морфофункциональный статус студентов-первокурсников смежных поколений на рубеже веков

The aim of this work was to carry out a comparative analysis of a series of anthropometric and physiometric parameters of students who studied in the first year of three faculties of Perm State Humanitarian Pedagogical University (PSHPU) in the academic years 2004/2005 and 2022/2023, that is, students belonging to two adjacent generations. The height and body weight, the blood pressure, the type of regulatory processes, as well as indices calculated on the basis of the listed parameters were compared: body mass index, or Quetelet's index (BMI), Functional Changes Score (FCS), Centralization Index (CI), Regulatory Effort Index (REI). The last two indices are derivatives of the parameters of heart rate variability (HRV), which make it possible to as-sess the contribution of autonomous and central regulatory circuits to the body processes and to predict the adaptive resources of the body. In both samples, there were the expected differences between the male and female participants in terms of weight and height parameters, e.g. the men were taller and heavier than the women, except for those whose BMI exceeded 25 kg/m2, i.e. overweight students. However, the students surveyed in 2022 did not demonstrate any differences in the values of the height and weight from those who studied in the same faculties in 2004. The assessment of the functional parameters did not show any significant differences between the generations of the late XX, early XXI century in the heart rate (HR), in the duration of the most frequent RR interval (Mo) and in the contribution of the autonomic and central regulatory circuits to the regulatory processes. What is alarming is the higher blood pressure, especially pulse pressure, which is a kind of marker of the vascular wall abnormalities in the large arteries. It was observed in students, especially young men, of a later generation, i.e. born in 2002-2004. HRV data indicate greater resistance of the women’s body to stressing factors. This can be concluded based on the influence of central and autonomous regulation circuits on the characteristics of heart rate: in the women, the autonomous regulatory processes were more intense than in men. Moreover, this fact was reported both in the sample of 2022 and among students examined in 2004.

STUDY OF CLINICAL PROFILE, SPIROMETRIC FUNCTION TEST, DIFFUSING CAPACITY OF CARBON MONOXIDE, 6 MINUTE WALK TEST AND CHEST X-RAY FINDINGS IN TEXTILE DYE-PRINTING WORKERS IN SURAT CITY

INTRODUCTION The textile industry consists of several processes including dyeing, printing etc. and due to the exposures to various chemicals at work, these workers frequently complain of respiratory symptoms. Spirometry allows us to measure FEV1,FVC, FEV1/FVC ratio,FEF25- 75%.Diffusion Capacity of Lung for Carbon Monoxide(DLCO) test indicates the diffusion of Carbon Monoxide gas across the alveolar membrane. In 6 Minute walk Test ,Pulse rate and SpO2 is measure at the start and at the end of the test. (At 0 min and at 6 min) and then fall or rise in Pulse or SpO2 is observed. METHODOLOGY This study included all the subjects according to the inclusion criteria(40) coming to Respiratory Medicine OPD during the study period (15 months). Data was collected and analyzed .RESULTS Majority of the patients were male, (50%) and smokers. Dry cough seen in – 29 patients (72.5%) & Dyspnoea on exertion in 15(37.5%) patients. Chest X-Ray was normal in – 21patients (52.5%), followed by Prominent Broncho-Vascular markings (BVM) was seen in 10(25%) patients. On Spirometry Findings, 24 (60%) patients were normal, 8 (20%) patients showed Restrictive Pattern, 6 (15%) showed Obstructive Pattern and 2 (5%) patients showed Mixed Pattern. In DLCO ndings, 27 patients showed normal (67.5%) and 13 (32.5%) patients showed Decreased Pattern. CONCLUSION Duration of exposure to dye and smoking were signicantly associated with Clinical features, reduced 6 Minute Walk distance, Abnormal Spirometry and DLCO ndings. FEF25-75% was signicantly decreased in most of the dye-workers in present study. As the Dyeing-workers are working in hazardous environment, there should protocols be formed for routine medical check-up at frequent interval in textile industry to detect occupation related diseases at early stage and to intervene the problem timely.

HM15912, a Novel Long-Acting Glucagon-Like Peptide-2 Analog, Improves Intestinal Growth and Absorption Capacity in a Male Rat Model of Short Bowel Syndrome.

Extensive bowel resection caused by various diseases that affect the intestines, such as Crohn's disease, volvulus, and cancer, leads to short bowel syndrome (SBS). Teduglutide is the only approved glucagon-like peptide-2 (GLP-2) drug for SBS; however, it requires daily administration. A novel GLP-2 analog with a prolonged duration of action to reduce dosing frequency and promote a greater efficacy may provide patients with a better quality of life. In the present study, the sustained exposure of HM15912 was characterized in normal male rats. The efficacy of HM15912 on intestinal growth and absorption capacity was also evaluated in normal male mice, rats, and SBS rats. HM15912 exhibited a remarkably extended half-life (42.3 hours) compared with teduglutide (0.6 hours) in rats. Despite somewhat lower in vitro potency on GLP-2 receptor than human GLP-2 or teduglutide, this longer-lasting mode of action promotes HM15912 to be more effective in terms of small intestinal growth than existing GLP-2 analogs even with a less frequent dosing interval of as little as once a week in rodents, including SBS rats. Furthermore, the small intestinal weight was approximately doubled, and the D-xylose absorption was significantly increased after pre-treatment of existing GLP-2 analogs on the market or under clinical development followed by HM15912 in rodents. These results indicate that HM15912 possesses a significant small bowel trophic effect driven by continuously increased exposure, supporting that HM15912 may be a novel treatment option with greater efficacy and the longest dosing interval among existing GLP-2 analogs for SBS with intestinal failure. SIGNIFICANCE STATEMENT: HM15912, a novel long-acting glucagon-like peptide-2 (GLP-2) analog, has a significant small bowel hypertrophic effect in rodents with a reduced frequency of administration compared to the existing GLP-2 analogs on the market or currently under clinical development. This study supports the possibility that HM15912 could be administered much less frequently than other long-acting GLP-2 analogs for patients with short bowel syndrome.

Bile acids as drivers and biomarkers of hepatocellular carcinoma.

The prevalence of hepatocellular carcinoma (HCC) is rapidly increasing, driven not least in part by the escalating prevalence of non-alcoholic fatty liver disease. Bile acid (BA) profiles are altered in patients with HCC and there is a developing body of evidence from in vitro human cellular models as well as rodent data suggesting that BA are able to modulate fundamental processes that impact on cellular phenotype predisposing to the development of HCC including senescence, proliferation and epithelial-mesenchymal transition. Changes in BA profiles associated with HCC have the potential to be exploited clinically. Whilst excellent diagnostic and imaging tools are available, their use to screen populations with advanced liver disease at risk of HCC is limited by high cost and low availability. The mainstay for HCC screening among subjects with cirrhosis remains frequent interval ultrasound scanning. Importantly, currently available serum biomarkers add little to diagnostic accuracy. Here, we review the current literature on the use of BA measurements as predictors of HCC incidence in addition to their use as a potential screening method for the early detection of HCC. Whilst these approaches do show early promise, there are limitations including the relatively small cohort sizes, the lack of a standardized approach to BA measurement, and the use of inappropriate control comparator samples.

The influence of different types of SCMs on microstructure and macroscopic properties of cementitious materials

In our study, the influence of different supplementary cementitious materials (SCMs) such as metakaolins, silica fume (microsilica) or filtered coal fly ash on the performance of concrete is discussed. The effects of different types and dosages of the SCMs have been investigated. Centrilit NC (MK1) and Metaver N (mk2) type metakaolins, Microsit® 20 (MS) type filtered coal fly ash or Centrilit Fume SX (SF) silica fume suspension was chosen as the replacement for the CEM I 42.5 N-SR0 sulphate resistant Portland cement. In addition to the two-component mixtures, we also examined the behaviour of the ternary blends, i.e. the combinations of SCMs. For the experiments, mortar prisms and cylindrical mortar specimens were prepared with water to binder ratio of 0.4. The paper presents the test results performed up to two years. The compressive strengths of the mixtures were examined. The most critical property of the cement-bound materials, the chloride migration coefficient of each mixture, was determined. The microstructure of the mixtures was determined by mercury intrusion porosimetry at the age of one year. Our results indicated (i) the best compressive strength was achieved for MK2 and for MK1 with combination of SF; (ii) the pore structure is much finer in the case of MK1 mixtures compared with those of MK2 or MS mixtures; (iii) the whole most frequent pore diameter interval falls into the range of medium capillaries only in case of MK1 (10 w%), for other mixtures the large capillaries are present in different extent. The SCMs greatly influence the extent of the enhancement in chloride migration coefficients with age: the less reduction was found for the mixtures of MK1, and the highest reduction was found for mixtures of MS. There is no direct function between the compressive strength, total porosity, specific surface of porosity or chloride migration coefficients.

Abstract CT125: A phase 1/2 randomized study of IGM-2323 in relapsed/refractory non-Hodgkin lymphomas

Abstract Background: Recent advances in the treatment of non-Hodgkin lymphoma (NHL) have transformed the landscape and provided significant benefits to patients. Novel agents that target CD19 and CD20 on B cells, such as bispecific T-cell engagers and chimeric antigen receptor (CAR) T cell therapy, have demonstrated benefit for patients in the relapsed and refractory setting. However, these agents can often be associated with significant toxicity and there is a need for new therapies that can provide clinical benefit while providing an improved safety profile.IGM-2323 is a novel CD20 x CD3 bispecific antibody utilizing an IgM backbone. This allows targeting of up to 10 CD20 binding sites for every CD3 site. In preclinical models, IGM-2323 demonstrated excellent antitumor activity with controlled T-cell activation. IGM-2323 is able to stimulate T cells at a more physiologic level than IgG-based antibodies, which may reduce adverse events typically associated with T-cell engagers and CAR-T, such as CRS and neurotoxicity. Methods: This study is a phase 1/2, multicenter, single-arm clinical trial of IGM-2323 monotherapy for patients with relapsed/refractory NHL. The Phase 1 component consists of a dose escalation and limited dose expansion evaluating multiple titration dose levels. As part of the titration dosing regimen, subjects receive weekly dosing on Day 1, 8, and 15 of each 21- day cycle. Dosing begins at 15 mg and is increased weekly for 3-4 weeks to reach the plateau dose. Patients then stay at the plateau dose until disease progression or unacceptable toxicity. Patients who achieve a response by Week 12 may switch to a less frequent dosing interval of every 3 weeks. The Phase 2 component will randomize patients at two different dose levels (100 mg and 300 mg plateau dose) in two separate indications (R/R DLBCL and R/R FL). Primary endpoints include frequency and severity of adverse events and objective response rate (ORR) based on Lugano criteria. Correlative biomarker studies will evaluate the correlation of clinical benefit with blood and tissue biomarkers. In Phase 2, there will be a formal analysis after 30 subjects are evaluable at each dose level and the best dose for each indication will be selected for further evaluation. The study is currently open with 47 patients enrolled at time of submission. Phase 2 is expected to begin enrollment in the first quarter of 2022. Clinical trial information: NCT04082936. Citation Format: Loretta Nastoupil, Elizabeth Budde, Won Seog Kim, Ajay Gopal, Chan Cheah, Ian Flinn, Gareth Gregory, Matthew Matasar, Catherine Diefenbach, Matthew Ku, Sung-Soo Yoon, Ibrahim Qazi, Rachel Wei, Maya Leabman, Genevive Hernandez, Iris Sison, Bruce Keyt, Thomas Manley, Phillipe Armand. A phase 1/2 randomized study of IGM-2323 in relapsed/refractory non-Hodgkin lymphomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT125.

Fire exclusion changes belowground bud bank and bud-bearing organ composition jeopardizing open savanna resilience.

Belowground bud bank regeneration is a successful strategy for plants in fire-prone communities. It depends on the number and location of dormant and viable buds stored on belowground organs. A highly diverse belowground bud-bearing organ system maintained by a frequent interval of fire events guarantees the supply of a bud bank that enables plants to persist and resprout after disturbance. We investigated how different fire exclusion and fire frequencies, affected the herbaceous layer in tropical savannas, by assessing belowground persistence and regeneration traits. Contrary to our hypothesis, we found that under a shorter fire exclusion period, the total bud bank increased at a lower fire frequency. But sites at longer fire exclusion and infrequent fire, the bud bank was smaller the longer the period since the last fire. However, the major shift was concerning organ diversity since fire exclusion was more related to loss of belowground diversity rather than decreasing of the belowground bud bank size. Furthermore, fire-associated bud-bearing structures like xylopodia disappeared in the fire suppressed areas, whereas clonal organs, such as rhizomes, developed in the bud bank. By quantifying belowground bud bank traits under different fire histories, we highlight the importance of the local fire regime on the composition of the belowground plant components, which can affect the tropical savanna aboveground plant community. Given that, loss of the belowground bud-bearing component of the plant community will have a direct effect on vegetation regeneration in post-fire environments, and consequently, on plant community resilience.

Colorectal Cancer Screening in Inflammatory Bowel Diseases—Can Characterization of GI Microbiome Signatures Enhance Neoplasia Detection?

Current noninvasive methods for colorectal cancer (CRC) screening are not optimized for persons with inflammatory bowel diseases (IBDs), requiring patients to undergo frequent interval screening via colonoscopy. Although colonoscopy-based screening reduces CRC incidence in IBD patients, rates of interval CRC remain relatively high, highlighting the need for more targeted approaches. In recent years, the discovery of disease-specific microbiome signatures for both IBD and CRC has begun to emerge, suggesting that stool-based biomarker detection using metagenomics and other culture-independent technologies may be useful for personalized, early, noninvasive CRC screening in IBD patients. Here we discuss the utility of the stool microbiome as a noninvasive CRC screening tool. Comparing the performance of multiple microbiome-based CRC classifiers, including several multi-cohort meta-analyses, we find that noninvasive detection of colorectal adenomas and carcinomas from microbial biomarkers is an active area of study with promising early results.

Basic life support: Awareness, attitude, and knowledge among junior doctors, physiotherapists, and nursing staffs in a tertiary care center of Sikkim

Background: Basic life support (BLS) is a lifesaving skill which every health-care personnel must know. It has been added to the curriculum but still studies have shown poor knowledge and skill among them in India. Aims and Objectives: The aim of our study was to assess attitude and knowledge of BLS among healthcare personnel in a tertiary care center of Sikkim and to recommend training of BLS according to the finding of our study. Materials and Methods: A questionnaire based cross-sectional study was done among junior doctors, physiotherapists, and nursing staffs, who were willing to participate. The questionnaire collected data under the heading of demographics, attitude, awareness, and knowledge about various domains of BLS. Analysis was done with standard statistical software. Results: Among 208 completed surveys, 24 (11.5%) were males and 184 (88.5%) were females, majority of them (76.4%) were nursing staff and belonged to 20–30-year age group (76%). Mean score of the participants were 13.43 ± 3.725 with a range from 2 to 21. The necessity of BLS training and the requirement of mandatory renewal was strongly agreed by 77.4% and 33.2% participants respectively. Conclusion: We conclude that they all need the trainings at frequent interval to know about the importance of BLS, to gain confidence and to improve their skill which will help them in timely saving of many lives in as well as outside the hospital. This can be achieved if institutes help in conducting the BLS session regularly despite being already in curriculum.