Intermediate Conditions Research Articles

Is Hybrid Work the Best of Both Worlds? Evidence from a Field Experiment

Abstract This paper reports causal evidence on how the extent of hybrid work—the number of days worked from home relative to days worked from office—affects employee attitudes and performance. Workers who spent around two days in the office each week on average self-reported greater work-life balance, more job satisfaction, and lower isolation from colleagues compared to workers who spent more or fewer days in the office. Employees in the intermediate hybrid condition received no different performance ratings compared to peers who spent more or fewer days in the office.

Effect of growth temperature on the microstructure and properties of epitaxial MoS2 monolayers grown by metalorganic chemical vapor deposition

Metalorganic chemical vapor deposition (MOCVD) is a promising technique for wafer-scale synthesis of MoS2 monolayers for 2D field-effect transistors (2D-FETs) and related devices. Epitaxial growth of MoS2 on sapphire provides films that are crystallographically well-oriented but typically contain low-angle grain boundaries (e.g., mirror twins), voids, and other defects depending on growth conditions and substrate characteristics. In this study, we investigate microstructure, optical properties, and field-effect characteristics of wafer-scale MoS2 monolayers grown by MOCVD on c-plane sapphire over a narrow window of growth temperatures (900–1000 °C). The density of low-angle grain boundaries in the MoS2 monolayer was found to decrease dramatically from 50% areal coverage for films grown at 900 °C to 5% at 1000 °C. This decrease in low-angle grain boundary density is correlated with an increase in the room-temperature photoluminescence intensity of A excitons and a decrease in the full-width-half maximum (FWHM) of the Raman A1g peak, which are typically indicative of a general reduction in defects in MoS2. However, the best transport properties (e.g., mean field-effect mobility mFE = 17.3 cm2/V s) were obtained in MoS2 monolayers grown at an intermediate temperature of 950 °C. It was found that as the growth temperature increased, small regions bound by high-angle boundaries begin to appear within the monolayer and increase in areal coverage, from ∼2% at 900 °C to ∼5% at 950 °C to ∼10% at 1000 °C. The growth temperature of 950 °C, therefore, provides an intermediate condition where the combined effects of low-angle and high-angle boundaries are minimized. The results of this study provide guidance on MOCVD growth and characterization that can be used to further optimize the performance of MoS2 2D-FETs.

Environmentally friendly assessment of ecological quality of watercourses based on banded demoiselle, Calopteryx splendens

AbstractDragonflies and damselflies are excellent bioindicators of the quality of both aquatic and terrestrial ecosystems. In our study, we assessed the usefulness of metric and meristic morphological traits as environmentally friendly and cost‐effective indicators of the integrative ecological quality of watercourses. Our study species of choice was the damselfly banded demoiselle, Calopteryx splendens (Harris) (Odonata: Calopterygidae). Adult C. splendens specimens were collected at three study sites along the trophic gradient of the Tisza River in Hungary and Ukraine. Body and abdomen length, head width, and distances between wing landmarks were assessed as metric traits, and the number of wing cells as meristic traits. The concentration of chlorophyll‐a was used to classify the three study sites into having a low, intermediate, and high trophic condition based on earlier studies. Significant differences were found along the trophic gradient based on the measured metric and meristic traits. Especially, insects from the site with the highest trophic condition had the largest body length, head width, and distances between wing landmarks, as well as the highest number of cells in the fore wings. There were also differences between males and females, but we did not find differences in fluctuating asymmetry (FA), i.e., differences between the left and the right wings. These results indicated that the morphological traits of adult banded demoiselles could be indicative of the environmental quality of a watercourse.

Null energy condition violation during inflation and pulsar timing array observations

Recently, evidence of stochastic gravitational wave background (SGWB) signals observed by pulsar timing array (PTA) collaborations, has prompted investigations into their origins. We explore the compatibility of a proposed inflationary scenario, incorporating an intermediate null energy condition (NEC)-violating phase, with the PTA observations. The NEC violation potentially amplifies the primordial tensor power spectrum, offering a promising explanation for PTA observations. Numerical analyses, primarily focused on NANOGrav’s 15-year results, reveal the model’s compatibility with PTA data. Notably, the model predicts a nearly scale-invariant GW spectrum in the mHz frequency range, which sets our scenario apart from other interpretations predicting a red primordial GW spectrum on smaller scales.

Topological phase transitions of generalized Brillouin zone

It has been known that the bulk-boundary correspondence (BBC) of the non-Hermitian skin effect is characterized by the topology of the complex eigenvalue spectra, while the topology of the wave function gives rise to Hermitian BBC with conventional boundary modes. In this work, we go beyond the known description of the non-Hermitian topological phase and find a different type of BBC that appears in generalized boundary conditions. The generalized Brillouin zone (GBZ) possesses non-trivial topological structures in the intermediate boundary condition between open and periodic boundary conditions. Unlike the conventional BBC, the topological phase transition is characterized by the generalized momentum touching of GBZ, which manifests as exceptional points. As a realization of our proposal, we suggest the non-reciprocal Kuramoto oscillator lattice, where phase slips accompany exceptional points as a signature of such topological phase transition. Our work establishes an understanding of non-Hermitian topological matter by complementing the non-Hermitian BBC as a general foundation of the non-Hermitian topological systems.

Association of chronic conditions and physical multimorbidity with new-onset incontinence in a nationwide prospective cohort study of older adults ≥ 50years in China.

The relationship between multimorbidity (i.e. ≥ 2 chronic conditions) and incontinence (i.e. urinary and/or faecal incontinence) is underexplored. This study investigated the association between multimorbidity and incident incontinence in Chinese adults aged ≥50years. Data from the 2011 and 2015 waves of the China Health and Retirement Longitudinal Study were used. The association between 12 chronic conditions, multimorbidity and new-onset incontinence was analysed using weighted logistic regression models. Mediation analysis was conducted to explore the potential mediators (self-reported health, subjective memory, depressive symptoms, disability, cognitive function, handgrip strength, mobility limitations, medications and frailty status) between multimorbidity and incontinence. Among 9,986 individuals aged ≥50years who were continent at baseline, 5.3% (n = 521) were newly incontinent 4years later (incident cases). The risk of incident incontinence increased with physical multimorbidity (OR 2.04, 95% CI 1.62-2.57). Compared to no chronic condition, having 1, 2, 3 and ≥ 4 chronic conditions were associated with incident incontinence with OR (95% CI): 1.41 (1.01-1.97), 1.74 (1.24-2.44), 2.82 (1.93-4.12) and 3.99 (2.29-6.95), respectively. The association between multimorbidity and incontinence was mediated by self-reported health (41.2%), medications (26.6%), mobility limitations (20.9%), depressive symptoms (12.8%), disability (11.6%), subjective memory (8.7%) and frailty status (8.3%). This longitudinal study found that physical multimorbidity and specific chronic conditions may increase the risk of new-onset incontinence among Chinese adults aged ≥50years. Self-reported health, medications and mobility limitations seemed to be important intermediate conditions between multimorbidity and incident incontinence.

Reversibility of linear cellular automata with intermediate boundary condition

<abstract><p>This paper focuses on the reversibility of multidimensional linear cellular automata with an intermediate boundary condition. We begin by addressing the matrix representation of these automata, and the question of reversibility boils down to the invertibility of this matrix representation. We introduce a decomposition method that factorizes the matrix representation into a Kronecker sum of significantly smaller matrices. The invertibility of the matrix hinges on determining whether zero can be expressed as the sum of eigenvalues of these smaller matrices, which happen to be tridiagonal Toeplitz matrices. Notably, each of these smaller matrices represents a one-dimensional cellular automaton. Leveraging the rich body of research on the eigenvalue problem of Toeplitz matrices, our result provides an efficient algorithm for addressing the reversibility problem. As an application, we show that there is no reversible nontrivial linear cellular automaton over $ \mathbb{Z}_2 $.</p></abstract>

Modelos matemáticos para ajustes na quantificação da volatilização de amônia do fertilizante ureia aplicado em pastagens tropicais

ABSTRACT: In Brazil, urea is the most used nitrogen (N) fertilizer to improve forage production. However, their excessive use can cause environmental impacts through N losses, such as ammonia (NH3) volatilization. Therefore, the current study adjusted and estimated the NH3 volatilization from urea applied on tropical pastures in three rainfall conditions using mathematical models. Data were collected from Marandu grass (Brachiaria brizantha) fertilized with 50 kg N ha-1 during wet, intermediate, and dry conditions. Ammonia volatilization was measured in five semi-open chambers for 21 days. The linear, quadratic, exponential, Gompertz, Groot, and Richards models were tested for fitting and estimating the NH3 volatilization. The Gompertz, Groot, and Richards models generated predictions similar to the observed data, with a high determination coefficient, indicating a better fit of these equations to data, with precision and accuracy. However, the Groot model was selected due to the lowest root mean square error of prediction (0.29 % total N lost as NH3). The greatest N loss as NH3 volatilization occurred in the wet, followed by intermediate and dry conditions (20.2, 17.0, and 11.3 % total N lost as NH3, respectively). Therefore, nitrogen losses as NH3 volatilization after application of 50 kg N ha-1, as urea source, are altered according to the weather conditions, reaching 20% of N added in the wet rainfall period. The Groot model is recommended for fitting and estimating the NH3 volatilization from urea applied on Marandu grass pastures in the wet and dry rainfall conditions.

Presenting a Conceptual Model Based on Cognitive Components and Personality Traits Affecting Entrepreneurial Competence through Document Analysis

Objective: Following the publication of a report on sustainable development issues, the United Nations identified creativity, innovation, and entrepreneurship as key elements to address sustainable development challenges. The primary objective of this study was to present an appropriate conceptual model for entrepreneurial competence based on cognitive components and personality traits with an emphasis on creativity. In this context, to achieve a comprehensive and hypothetical understanding of the psychological factors' impact on entrepreneurship, an integration of both the creativity and entrepreneurship domains was utilized. Methods and Materials: This study employed a qualitative meta-synthesis approach. According to the qualitative meta-synthesis method, the research population included all Persian and English scientific documents (research articles, theses, and books) published in the field of entrepreneurship from 2010 to 2022. To assess the quality of the found articles, the impact factor of a scientific journal was examined, and 90 articles were approved. Then, the relevant data from each article were extracted and entered into MAXQDA software. After reaching saturation, content analysis in this software was a systematic and continuous process of data comparison, conducted in three stages: open coding, axial coding, and selective coding, based on Strauss and Corbin's approach. Findings: The results showed that the conceptual model of entrepreneurial competence based on cognitive components and personality traits with regard to creativity includes the following: Personality traits (dynamism and restlessness, lively interaction and humor combined with personal discipline, thoughtful extraversion, ambition with altruism, simultaneous femininity and masculinity, rebellious and independent, passionate yet realistic and goal-oriented, suffering and pain along with much pleasure, determined and serious yet flexible, internal control source, openness and the expansiveness of fantasy rooted in realities, emotional stability with emotional steadiness, hardworking and perseverance combined with responsibility). Cognitive components (intelligence quotient above 120, active memory, attention and concentration, convergent and divergent thinking), Contextual conditions (planning ability, organizational ability, time management and control, reasoning power, judgment ability, decision-making power, problem-solving ability, impulse control), Intermediate conditions (cognitive flexibility, ambiguity and conditions of uncertainty and certainty, being active, experience-seeking and risk-taking). Conclusion: It can be concluded that a multidimensional empirical approach of cognitive components and personality traits provides more information.

Ritual schedule and worshippers’ origin at an ancient Maya ritual cave site, Las Cuevas, Belize: a pilot study of jute snail shell sclerochemistry

Sequential stable carbon and oxygen isotope data were measured on 15 jute snail shells (Pachychilus sp.) excavated from the Cave at Las Cuevas, a ritual cave site in western Belize. The shells were found intact in the undisturbed, excavated ritual activity area, suggesting they were left as offerings, not as food waste. The offering of jute snails is thought to be associated with ancient Maya concern for rainfall needed for agriculture, thus the interpretation of the isotope data focused on assessing if the shells were offered in rainy or dry periods. Seven of the shell profiles did not contain oscillations in isotope profiles, and so could not be interpreted for wet or dry season of capture. The remaining shells’ isotope profiles indicate some were captured in rainy, dry, and intermediate conditions. Significant variation in the ranges in absolute carbon and oxygen isotope values suggest they were collected from two or more locations, therefore at least some of the snails were brought in from a distance rather than collected locally prior to offering. More detailed conclusions cannot be confidently made without additional method validation studies, but this project supports the potential utility of jute shell sclerochronology in Maya archaeology.

Energy States of an Exciton in Truncated Paraboloid in the Intermediate Confinement Conditions

Energy States of an Exciton in Truncated Paraboloid in the Intermediate Confinement Conditions

Recommended control options of a daylight dimming system for daylit perimeter zones of open-planned office with curtain walls

This study investigates control options of a daylight dimming system in an open-planned office for required lighting environments with lighting energy savings and acceptable glare ratings. Computer simulations were performed for photosensors with three ranges of viewing angles in two daylit perimeter zones of the office and consecutive computational processes based on dimming control algorithm were employed for final light output of lighting fixtures. Three CIE standard sky and blind conditions were employed for the prediction of indoor daylight illuminance, photosensor illuminance, and daylight glare probability (DGP). The results indicate that the perceived glare can be imperceptible for the majority of time periods and a daylight dimming control system can be effectively applied for perimeter zones of office with curtain walls. For the south-facing zone under clear and intermediate sky conditions, the horizontal and 45 degree blind conditions are recommended to be combined with the full or partial photosensor shielding conditions for desirable dimming control performances. The unshielded photosensor condition should be generally avoided. For the east-facing zone under clear and intermediate sky, the photosensor sensing range should be narrowed using full shielding for the improvement of system performance of daylight dimming control. The unshielded and partially-shielded photosensors are rarely recommended. For the east and south-facing zone under overcast sky, effective control performance was rarely achieved due to the lack of daylight. Predictions models for linear relationships between the workplane and photosensor illuminances due to daylight were statistically acceptable, and strong relationships existed between them.

Bisantrene in Combination with Fludarabine and Clofarabine As Salvage Therapy for Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML)- an Open-Label, Phase II, Study

Background: Bisantrene (Bis), is a topoisomerase-II inhibitor with anthracycline-like activity, lower cardiotoxicity, and activity in patients (pts) with relapsed (rel)/primary refractory (PR) acute myeloid leukemia (AML) (Am J Hematol, 2021). Bis was also found to synergize with the cytotoxic purine nucleoside analogs clofarabine (Clo) and fludarabine (Flu) in vitro (J Clin Exp Oncol, 2021). We now conducted a phase II study combining Bis with Clo and Flu in pts with Rel/PR AML (NCT04989335). Methods: This was a phase II open-label single-center study with 2 stages: a stage with 3+3 dose escalation to assess the safety and provide phase 2 dose (RP2D, 4 vs 5 days) of infusion (i.v.) with up to 12 pts and an expansion phase with up to 17 pts (Simon 2-stage design 9+8) to assess the primary efficacy and confirm the safety of f Bis/Clo/Flu combination pts with Rel/PR AML. Flu (10 mg/m 2) was administered i.v. over 1 hour (h), followed by a 1-h infusion of Clo (30 mg/m 2), and then a 2-h infusion of Bis at 250 mg/m 2, with a 1-hour break for 4 days. The primary endpoint was achieving a partial response (PR). Efficacy was assessed by bone marrow (BM) examination 21 - 30 days post-therapy. Safety included treatment-emergent adverse events (TEAEs), all-cause mortality, and cardiac monitoring with ECG and troponins Toxicity was assessed as per Common Terminology Criteria for Adverse Events (CTCAE v5.0). Interim analysis was planned after the first 12 pts. Results: 20 pts were included from August 2021. The median age was 48 (19-69) years and 55% were male.14 pts had de novo AML and 5 had secondary AML, 11 pts were in rel, while 9 had PR disease. Median lines of therapy were 4(3-9), 12 with ≤ 4 and 8 >4 lines of therapy. All pts were refractory to the last line of therapy.15 pts (75%) were in relapse post allogeneic transplantation (HSCT). 5 (25%) pts had active extramedullary disease (EMD, 1 with CNS involvement). Median bone marrow blasts pre-Bis/Clo/Flu treatment was 50%. Cytogenetic was normal in 10 (50%) of the pts, 5 had a complex karyotype, 2 MLL rearrangements, 1 t8; 21 and 2 pts had other chromosomal abnormalities. The maximum tolerated dose of the Bis/Clo/Flu combination was 4 days of infusion due to grade 3 liver toxicity in 2 pts and 1 pt that died from sepsis in the first stage of the study. Overall 10 pts developed liver toxicity with elevated liver enzymes and bilirubin in 9 of them (grade 1-4 pts; grade 2-3 pts and grade 3-3 pts). Liver toxicity was transient and resolved in all pts. Two pts had treatment interruption due to liver toxicity. 4 pts had grade I renal toxicity, 7 had mild fluid retention, and 18 developed neutropenic fever of which 10 pts had verified bacteremia. Five pts had pneumonia, 4 invasive fungal infections, and 2 sepsis (1/2 died).1 additional pt died from cerebral venous sinus thrombosis. Overall 5 pts died early and could not be evaluated for response. Clinical-relevant cardiac toxicity was not observed in any of the pts and no one developed ECG changes Transient grade 1 elevation of troponin levels was observed in 4 pts. Six pts responded (CR-5, PR-1) 3 with EMD, however, responses were short-lived and lasted up to 3 months. Five pts (responding-4, active disease-1, being the second transplant in 4) underwent HSCT 1-3 months post-Bis/Clo/Flu with reduced /intermediate intensity conditioning. Stem cell donors were haploidentical-2, matched unrelated -1, and matched sibling-2, respectively. Three pts died: one from graft versus host disease and the other from relapse within 4 months post-transplant and the third from sepsis 2 years post-HSCT. Two of the transplanted pts are in complete remission with a 2-month follow-up. Conclusions : In this Phase II study in a very advanced group of relapsed refractory AML ptsresistant to multiple previous lines of chemotherapy including transplantation and with a median of 50% blasts at study initiation, Bis/Clo/Flu combination therapy was found to be safe and well tolerated without cardiac toxicity or tumor lysis syndrome. The maximum length of Bis/Clo/Flu administration was 4 days due to rapidly reversible liver toxicity, and transaminitis. As expected in this highly pretreated population, the infection rates were high. Six /15 evaluable pts (40%) respond, enabling an HSCT in 5 of them. These rather impressive results in such a heavily pretreated population support further studies of Bisantrene-based combinations, including those with venetoclax or hypomethylating agents.

Zinc Status Affects T Cell Reconstitution in Patients Receiving Naïve T Cell Depleted Allogeneic HSCT

Delayed immune reconstitution (IR) is a major clinical problem contributing to post-allogeneic hematopoietic stem cell transplant (allo-HSCT) morbidity and mortality. Specifically, CD4 T cell reconstitution is linked with improved clinical outcomes. As the primary organ of T cell production, the thymus is a crucial contributor to T cell reconstitution after HSCT generating a broad T cell receptor (TCR) repertoire selected through central tolerance However, T cell reconstitution can be hindered by poor thymus function as a consequence of age, transplant conditioning, or graft versus host disease (GVHD). At present, no drugs are available to boost T cell recovery, while many of the factors limiting IR are still unknown. Zinc (Zn), the second most abundant trace element in our body, is important for normal T cell development. Zn deficiency (ZD) in humans and mice is characterized by poor circulating T cells and depressed thymic function, which are both restorable after reintroduction of Zn with the diet. Despite having multiple risk factors for ZD, there are no published data focusing on ZD prevalence among allo-HSCT recipients. Based on our previous observations, we hypothesized that peri-HSCT Zn levels correlate with IR. In this study, we analyzed serum Zn levels of allo-HSCT patients who received naïve T cell (T N) depleted grafts as a strategy to prevent aGVHD (Bleakley et al., 2022, NCT00914940). This population is particularly interesting for studying IR because in these patients, circulating T N at d+365 after HSCT will primarily be of donor hematopoietic stem cell origin generated in the recipient thymus. Samples and clinical data were prospectively collected. Fifty-two patients had peri-HSCT serum samples available for Zn measures, as pre-HSCT and/or day +80 samples. Zn measures were performed through mass-spectrometry at the University of Washington Hospital-Biochemistry Lab. ZD was defined for Zn<70ug/dL as defined by the WHO. T cell populations (CD4 +, CD8 +, T N CD4 + and CD8 +, T regulatory cells, NK cells, B cells) were analyzed by flow cytometry at day+365. DNA was extracted from PBMC pellets collected at d+365 and were analyzed in qPCR for the expression of signal-joint T cell receptor excision circles (sjTRECs), being the gold standard for measuring thymic-derived T cells. We studied the association between Zn levels at baseline and day+80 and parameters of IR through linear regression. Comparisons between two groups were analyzed by t-test. Median age at transplant was 47 (range 6-61). Twenty-eight patients received myeloablative conditioning with total body irradiation (TBI) of 13.2 Gy (53.8%) and 24 (46.2%) received an intermediate intensity conditioning regimen with 4Gy TBI. Forty-one patients (78.8%) had pre-HSCT and 46 (88.5%) had day+80 Zn measures; 38 patients (73.1%) had both pre-HSCT and day+80 Zn measures. Median pre-HSCT and day+80 Zn levels were, respectively, 71 (range 60-105) and 80 (range 36-112); at baseline, 13 patients (25%) had ZD (<70ug/dL, according to WHO), whereas seven (13.3%) were ZD at day+80. Median sjTRECs at day +365 were 3.33/mg of DNA (range 0.00-16,704.54). As expected, sjTRECs at day+365 significantly correlated with age at transplant (r 2=0,3824; p<0.0001), whereas Zn levels preHCT or day80 did not. The number of circulating CD4 + and CD8 + T N at day+365 showed significant correlation with age. Zinc levels did not correlate with IR of absolute CD4 +, CD8 +, NK, T regs, and B cells at day+365, although we observed a trend for lower CD4 + counts at day 365 with lower day+80 Zn levels. Day+80 serum Zn levels was associated with sjTRECs at day+365 (Figure 1A. r 2=0.2643; p=0.0019) and lower pre-HSCT Zn significantly correlated with worse CD8 +T N reconstitution at day+365 (Figure 1B. r 2=0.1433; p= 0.0327), with clear trends in the same direction also for pre-HSCT Zn and CD4 + T N and day+80 Zn and CD4 + T N. In conclusion, we found that a non-negligible population of patients undergo allo-HSCT with unrecognized ZD. Peri-transplant Zinc status negatively affects IR, especially on the thymic-derived T cell compartment. Early recognition of ZD and zinc supplementation might help prevent morbidity related to poor IR in a proportion of patients. A multivariable analysis looking at other clinical data and outcomes is ongoing. Validation of these findings is needed on a larger number of patients, including a cohort of patients receiving T N-replete HSCT.

Pure/combined buckling mode calculation of thin-walled members constraining general shell FE models

This paper proposes a technique for decomposing the buckling solution of thin-walled members into pure deformation modes (global, distortional, local, or other), aiming at providing an insight into the buckling behavior of these members. The calculation of critical loads associated with a specific or combined deformation mode is performed constraining general finite element models. A general constraining procedure is presented, in which the critical load of any mode, combining different section deformation modes and different harmonic shape functions in the longitudinal direction, can be determined. Cases where all possible harmonic terms may be automatically considered are also described. Cross-section deformation modes are defined in the context of the constrained finite strip method (base vectors), and the proposed constraining procedure is implemented by means of relationships between degrees of freedom of the finite element mesh in commercial software. Calculation of combined buckling modes inherently makes it possible to quantify the participation of the considered modes, including along specific longitudinal segments of the member. Results from the analysis of a lipped channel member are presented to demonstrate the concepts and, later, the analysis of a member with a more complex cross-section and intermediate boundary conditions along length is detailed. A discussion on the base vectors chosen for the constraining method is presented. Finally, the potential of the proposed method is discussed.

Centrifuge modelling of axially loaded steel piles in cold and thawing frozen sand

Foundations in northern climates are founded under ground conditions that are certain to change due to climate warming. Piled foundations situated in permafrost are designed to resist loads by mobilising the shaft friction from adfreeze strength that is attributed to the ice–soil bonds in contact with the pile. Design considers ground warming causing thawing over time and normally specifies a thermal condition whereby mitigation measures, such as thermosyphons, need to be implemented. While pile design and analysis for completely frozen and thawed profiles are defined in terms of pile capacity, the intermediate condition, during transition from frozen to thawed, is not well examined. In this study, centrifuge modelling is utilised to quantify the reduction in pile capacity and foundation stiffness under an axial monotonic loading as initially frozen sand profiles warm and thaw depth increases. The results show agreement between the physical models and analytical methods for piles in fully frozen and thawed ground. A marked decrease in pile capacity occurs as ground temperatures approach freezing and thaw depth increases. The results are the first comprehensive physical model testing programme aimed at quantifying pile performance in frozen and warming ground under field-realistic stress conditions.

Expression of Budding Uninhibited by Benzimidazole Related-1 and Telomerase in Perilesional Area of Oral Squamous Cell Carcinoma

Objective: The premalignant lesions are regarded as intermediate conditions for subsequent cancer development. Even clinically, normal-appearing mucosa could harbor early precancerous genetic mutations. This study determines the immunohistochemical expression of Budding uninhibited by benzimidazole r elated-1 (BubR1) and Telomerase in the perilesional area of oral squamous cell carcinoma. Materials and methods: The study involved thirty-three formalin-fixed paraffin embedded blocks of the perilesional area of oral cancer. The stain distribution, subcellular localization, and intensity of these two markers in response to their cellular localization were d etermined and then related to Byrne’s grading system. Fisher’s exact test and spearman’s rho test were applied to a nalyze the data. P≤0.05 is considered significant. Results: BubR1 showed prominent, continuous distribution in the full thickness of perilesional samples (54.5%). The subcellular localization of BubR1 was significantly related to Byrne's grading system (P≤0.001). High discontinuous distribution of telomerase throughout the epithelia was detected (63.6%). Byrne's grading system showed high significant relations to both stain distribution and subcellular localization of telomerase, as P- values were .001 and .002, re spectively. Both markers showed high significant full thickness localization of buccal mucosa. Conclusions: Both makers overexpression through multiple layers of oral epithelia in the perilesional area might determine their valu able role in the early detection of oral cancer. Furthermore, the significant mixed subcellular localization of these markers in high-grade cancer could delineate their combined role in developing the second primary tumor.

Assessment of endocrine function in males with pre-diabetes

Introduction and Aim: Diabetes mellitus is associated with various endocrine derangements and prediabetes is an intermediate condition between health and full-fledged disease state. Hormones of Hypothalamus-Pituitary-Thyroid (HPT), Hypothalamus-Pituitary-Adrenal (HPA), Hypothalamus-Pituitary-Gonadal (HPG) axes and pineal gland were studied in males (n=105) with prediabetes.
 
 Materials and Methods: Based on fasting plasma glucose (FPG), the subjects were categorized as healthy controls, prediabetes, diabetes and various hormones were compared between these three groups.
 
 Results: Insulin levels showed a systematic increase from pre-diabetes to diabetes subjects. HPT axis had a semblance to “Primary hypothyroidism” with an increase in Thyrotropin-releasing-hormone (TRH), Thyroid-stimulating-hormone (TSH) and decrease in fT4 and fT3 with rise in glucose levels. HPA axis detected high Corticotropin Releasing Hormone (CRH), Adrenocorticotropic hormone (ACTH), cortisol in the overtly diabetic group while prediabetes values were comparable to control. The HPG axis demonstrated significantly high Gonadotropin-hormone-releasing-hormone (GnRH) in the diabetic group but not in the prediabetic. A graded increase in LH and significant decrease in testosterone and melatonin was observed with a rise in FPG.
 
 Conclusion: Thus, it could be concluded as endocrine gland damage due to hyperglycemia and hyperinsulinemia causes multiple endocrine dysfunctions in prediabetes that aggravates, as the patient turns diabetic.

Optimized Double-Unit Cord Blood Transplantation Mitigates Transplant-Related Mortality Resulting in High Progression-Free Survival in Adults with Hematologic Malignancies

Background : Double-unit cord blood transplantation (dCBT) with intermediate intensity conditioning (Cy50/ Flu150/ Thio10/ TBI400cGy) and cyclosporine-A (CSA)/ mycophenolate mofetil (MMF) graft-versus-host disease (GVHD) prophylaxis has been associated with high progression-free survival (PFS) in adult patients (pts) with hematologic malignancies ( Barker JN et al, Blood Advances 2020). Now, our Center has investigated multiple refinements to further mitigate transplant-related mortality (TRM). Herein, we have analyzed transplant outcomes in these adult dCBT pts to establish an optimized dCBT platform. Methods : Consecutive adult first allograft pts with high-risk hematologic malignancies who underwent first allografts with intermediate intensity dCBT between 3/2018-8/2022 were analyzed. Optimizations involved further refined unit selection placing highest priority on unit quality (i.e. optimized banking practices) & CD34+ cell dose over HLA-match, ensuring therapeutic (CSA) levels (> 250 ng/mL) by day 0, prompt treatment of pre-engraftment syndrome (PES) & letermovir prophylaxis in CMV seropositive pts from day +7. Also, we have investigated 2 strategies to mitigate acute graft-versus-host disease (aGVHD): pts early in the study period received CSA, MMF & tocilizumab (8 mg/kg on day -1) prophylaxis ( Toci Group), whereas recent pts ( Recent Group) received CSA/ MMF with prompt therapy of clinically diagnosed aGVHD. Results : Of 74 patients (Table), 49 were in the Toci Group, & 25 in the Recent Group. Most pts were transplanted for acute leukemia (n = 55, 74%) & over half (n = 39, 53%) had non-European ancestry. Distribution of diagnoses, CMV serostatus, HCT-CI & graft characteristics were similar between the groups but Recent Group pts tended to be younger (38 vs. 47 years, p = 0.071). Toci Group pts had delayed neutrophil recovery [engraftment incidence 94% (95%CI: 87-99) at a median of 25 days (range 16-40), one graft failure], but low rates of PES (n = 19, 39%). The day-100 incidence of grade II-IV & III-IV aGVHD were 69% (95%CI: 56-82) & 10% (95%CI: 2-19), respectively. One pt (false negative CMV-serostatus) who did not receive letermovir had CMV infection. One-year TRM was 16% (95%CI: 6-27) with a 1-year relapse rate of 6% (95%CI: 3-13). TRM was due to infection (n = 3), aGVHD (n = 3, 1 with concurrent COVID-19 infection), multiorgan failure (n = 2) & graft failure (n = 1). With a median follow-up of 47 months (range 28-62), the 1-year OS was 84% (95%CI: 73-94) & 1-year PFS was 78% (95%CI: 66-89). By contrast, the engraftment incidence in Recent Group pts was 100% with a faster median neutrophil recovery of 19 days (range 11-36, p = 0.002) & all engrafted platelets at a median of 36 days (range 24-92). However, most Recent group pts developed PES [n = 20 (80%), p < 0.001] although this responded promptly to short course corticosteroids. Day 100 grade II-IV aGVHD was also higher [92% (95%CI: 81-99), p = 0.009], although grade III-IV aGVHD was low [8% (95%CI: <1-19)] & similar to tocilizumab pts. Day 100 incidence of CMV was 0%. With a median follow-up of 17 months (range 6-50), the 1-year TRM in Recent Group pts is 0% with a 1-year relapse incidence of 13% (95%CI: 7-27). Consequently, the 1-year OS & PFS are high at 96% (95%: 89-99) & 87% (95%CI: 74-99), respectively (Figure). Conclusions: Optimized dCBT with intermediate intensity conditioning, graft selection that prioritizes unit quality & CD34+ dose, CSA/ MMF prophylaxis with prompt therapy of PES & aGVHD, & letermovir CMV prophylaxis mitigates TRM in young & middle-aged adults. Thus, combined with relatively low relapse rates, the PFS & OS are high. Tocilizumab has been abandoned due to its notable association with delayed neutrophil engraftment & lack of survival advantage. Letermovir is highly effective completely preventing CMV infections & may contribute to the reduced aGVHD-related mortality recently (as compared to the pre-tocilizumab era), since avoidance of CMV antiviral therapy toxicities greatly facilitates aGVHD prevention & therapy. Given the rapid availability of cryopreserved unmanipulated CB grafts & frequent limitations of URD availability for minority populations, optimized dCBT is a highly attractive curative therapy for acute leukemias & other high-risk myeloid malignancies warranting prospective multi-center investigation.

High Progression-Free Survival with Low Relapse Rates after Double-Unit Cord Blood Transplantation in Patients with High-Risk AML

Background : Double-unit cord blood transplantation (dCBT) is standard therapy for patients with acute myelogenous leukemia (AML) who do not have suitable adult donors. We & others have reported low relapse rates & high progression free survival (PFS) in dCBT recipients suggesting robust CB-derived graft-versus-leukemia effects. However, the efficacy of dCBT in high-risk AML as determined by ELN genetic risk & pre-transplant minimal residual disease (MRD) status has not been performed to date. Methods : All consecutive adult patients with AML who received first dCBT with intermediate intensity conditioning (Cy50/ Flu150/ Thio10/ TBI400) between 2014-2022 were analyzed. GVHD prophylaxis was with either Cyclosporine-A (CSA)/ Mycophenolate Mofetil (MMF) or CSA/MMF/Tocilizumab on an institutional protocol. Results : 63 patients (pts) (median age 49 years, range 23-63) were eligible for analysis (Table); 42 (67%) were CMV seropositive, 31 (49%) had non-European ancestry, & median HCT-CI was 2 (range 0-6). Most (n = 55, 87%) were in CR1, 5 (8%) in CR2, & 3 were relapsed or primary refractory at transplant (5-9% blasts). By ELN2022 genetic risk criteria, 8 pts had favorable, 29 intermediate, & 20 adverse risk AML (6 were missing ELN status). Of the 60 pts in CR, 36 were MRD- & 18 MRD+ by multicolor flow cytometry (6 had unknown/ indeterminate MRD status). Sixty-one of 63 pts engrafted for a 60-day cumulative incidence of 98% (95%CI:81-100). The median follow-up of survivors was 58 months (range 8-104 months). The 1- & 3-yr incidences of transplant-related mortality (TRM) were 13% (95%CI: 5.9-22) & 18% (95%CI: 9.6-29), respectively. The 1- & 3-year relapse incidences were 3.2% (95%CI: 0.6-9.9) & 8.6% (95%CI: 3.1-18), respectively. The 1- & 3-year OS were 87% (95%CI: 79-96) & 82% (95%CI:72-92) respectively, whereas the 1- & 3-year PFS were 84% (95%CI: 76-94) & 73% (95%CI: 63-85), respectively. When stratified by ELN2022 genetic risk, the 3-year relapse incidence was 0% in favorable, 10% (95%CI: 2.5-25) in intermediate & 13% (95%CI: 2-36%) in adverse risk AML patients. Pts with favorable risk AML had a 3-year PFS of 88% (95%CI: 67-100); the 3-year PFS was similar in patients with intermediate [68% (95%CI: 53-88)] or adverse [67% (95%CI: 48-93)] risk AML (Figure 1A). When stratified by MRD status, the 3-year relapse incidence was 8.4% (95%CI:2.1-20) in MRD- & 13% (95%CI: 1.9-34) in MRD+ patients. The 3-year PFS was similar in patients with AML in CR who were MRD- 80% (95%CI: 68-94) or MRD+ 76% (95%CI: 57-100), whereas all 3 relapsed/ refractory patients died of TRM (Figure 1B). Of 4 TP53-mutated AML patients, one relapsed, one died of TRM, & two are alive in remission. Conclusions: While retrospective, our findings highlight the low relapse rates & promising PFS in adult AML patients, including those with high risk features such as adverse-risk ELN genetic risk &/ or MRD positivity supporting robust CB-derived graft-versus-leukemia (GVL) effects. This observation, together with the mitigation of TRM in recent years due to the optimized transplant practices in adult dCBT (see Politikos et al, ASH 2023), makes intermediate intensity dCBT an attractive strategy for AML patients with a suitable dCB graft & high-risk disease. Our findings warrant prospective multi-center investigation with correlative studies to elucidate the biology of CB-derived GVL.