Duration Of Occupation Research Articles

Impact of Socio-Demographic Factors on Quality of Life and Coping Strategies of Children with Different Disabilities.

Background and Objectives: Children with disabilities face unique challenges that can affect their well-being and quality of life (QOL). This study aimed to assess the QOL and coping strategies adopted by children with disabilities and explore how socio-demographic factors influence QOL and coping strategies. Materials and Methods: This cross-sectional study, which was conducted in Saudi Arabia with children aged 6 to 18 years, used a stratified random sample to ensure representation from a variety of demographic groups. Short Form-12 (SF-12) was used to assess the QOL in the sample population. The Brief COPE Inventory was used to examine coping strategies among the children. One-way analysis of variance was applied to examine differences in the QOL, coping strategies scores, and demographic variables. Multiple regression analyses were performed to examine the role of demographic variables in predicting QOL and p value was considered statistical significance at p < 0.05. Results: The results of the study clearly revealed significant differences between the mean scores of QOL for gender, age, and type of disability, duration of disability, education qualification, family status, family occupation, and housing status. Female participants showed better QOL in physical functioning than their male counterparts. Children with intellectual disability reported better QOL in general health, vitality, social functioning, and mental health. Participants with seven to eight years of disability reported higher scores in physical functioning, vitality, and mental health. Children whose parents were working in private agencies and living in rented houses scored higher on the general health aspects of quality of life. The findings also revealed that the duration of the disability was a significant predictor of the QOL. The mean scores of different dimensions of coping strategies clearly revealed that male participants used dysfunctional coping (p < 0.01), as compared to problem-focused and emotional-focused coping while female children relied more on emotional-focused coping. Emotion-focused coping was significantly higher in participants with visual (p < 0.01), learning (p < 0.01), and intellectual disabilities (p < 0.01). Dysfunctional coping scores were higher among children with auditory disabilities (p < 0.01) and multiple disabilities (p < 0.01). Conclusions: This study highlights the significance of demographic factors in understanding and improving the well-being of a diverse population of disabled juveniles. It offers valuable insights into the subtle factors affecting quality of life. Future interventions and policies can leverage these findings to enhance the quality of life of individuals with disabilities and to foster a more supportive and inclusive approach.

Urban agrarian reform: opportunities and challenges for land rights among low-income communities

Agrarian reform has typically focused on the redistribution of land in rural areas, specifically targeting farmers and agricultural tracts of land. This study explores the potential for agrarian reform in urban settings and the challenges facing low-income individuals in acquiring land rights essential to adequate housing. Using statutory and theoretical perspectives demonstrates that ample opportunities still exist for urban agrarian reform to take hold via the expropriation of state-owned land and land whose rights have lapsed. Public land that has not been dedicated as a waqf or even recognized as government property and historic land rights where the building rights expired and without any application to extend those rights present empirical reform opportunities. Despite these opportunities, urban land rights remain a contested space. Many poor people live on untitled land because such a thing is considered disputed by public authorities. Conflicts arise from the physical duration of inhabitants' occupation, which is in severe contrast to claims found with entities holding either outdated or inadequate property documentation. The official bodies, particularly the Land Office, are hesitant to issue land certificates due to these conflicts. The uniqueness of this research lies in its focus on urban land reform and its implications for the poor, thus highlighting a gap in existing literature that focuses largely on rural settings. This important research study depends on the emerging need for appropriate and certain housing options in cities. The importance of this study to the discipline is that it fosters the application of national land law principles, namely equity, legal certainty, and practicality, to disputes over urban land, providing a framework for a fairer distribution of land rights.

Evaluating radon concentration and temporal correction factors in residential and workplace buildings: A comparison of passive and active methods

Effective mitigation of the health impacts of radon exposure begins with accurate measurement of this environmental contaminant. Typically, radon surveys require measurements over a period of several months. This process involves the application of temporal correction factors (TCF). Disparities in indoor radon concentration (IRC) are evident across building types. While the integrated technique has traditionally been considered the most reliable for measuring IRC, the active method is becoming more prevalent due to the availability of commercial radon measurement instruments. The aim of this study is to compare IRC using passive (CR-39) and active (ICA device) methods across 69 indoor spaces, including 35 workplaces and 34 residential buildings. The investigation was conducted over a span of one year and included 966 CR-39 detectors that were replaced every 3 and 6 months, respectively, to assess seasonal fluctuations and facilitate the computation of TCF. Statistically significant differences in IRC were observed between residential and workplace buildings (p < 0.001). Among workplaces, educational and research institutions showed the highest average IRC (166 Bq/m3), while hospitals exhibited the lowest (25 Bq/m3). Significant differences in TCF were found between the two measurement methods (p < 0.05), making TCF specific to the passive method inapplicable to active method. Moreover, distinctions between workplace and residential buildings, including the presence of air conditioning units and differing occupancy patterns, lead to substantial differences in both IRC (p < 0.001) and TCF. The assessment of radon exposure based on room occupancy duration revealed substantial variations: workplaces showed lower actual exposure (62 Bq/m3 vs. 75 Bq/m3, p < 0.001), while residential settings, particularly at night, displayed higher exposure (278 Bq/m3 vs. 245 Bq/m3, p = 0.02) than integrated measurements suggest. Continuous monitoring systems offer critical insights into true radon exposure levels.

Transfer and persistence of intruder DNA within an office after reuse by owner

The heightened sensitivity of DNA typing techniques, paired with the extensive use of trace DNA in forensic investigations, has resulted in an increased need to understand how and when DNA is deposited on surfaces of interest. This study focussed on the transfer, persistence, and prevalence of trace DNA in a single occupation of an office space by an intruder, when all contacts made during occupation and for the two hours prior and post occupation were known. The extent to which DNA could be recovered from contacted/not contacted surfaces was investigated. This study investigates the impacts of these movements and use of an office space when the duration of occupancy, surface contact histories and shedder status of participants are known. Contacts were documented and surfaces in the office space were targeted for sampling. Categories were set for target sampling that included different types of contact. Direct and indirect DNA transfer was detected in 55 % and 6 % of samples, respectively. Contactless DNA transfer was detected in 0.5 % of samples. The owner was observed as the sole/major/majority contributor in 77 % of the samples and as minor contributor in 10 % of samples. The intruder was observed as the sole/major/majority contributor in 14 % of samples and as the minor contributor in 16 %. An increased number of contacts increased the relative DNA contribution of the individual making the contact, however, not all observed direct contacts resulted in detectable DNA transfer. The outcome of this study will aid in better sample targeting strategies and contribute to the pool of data assisting in the development of activity level assessments.

Rethinking Occupation Intensity during the Levantine Middle Epipalaeolithic: The use of Space and Site Formation Processes at the Geometric Kebaran site of Neve David, Israel

AbstractThe open-air Epipalaeolithic (Geometric Kebaran) site of Neve David (Mount Carmel, Israel) has played an important role in reconstructing scenarios of sedentarization in the Levant since its initial excavation in the 1980s, and has been seen as heralding later Natufian socioeconomic adaptations. However, little was known about the site’s formation processes and spatial organization, hindering the testing of this view. Employing new field data from Neve David, we present a combined macro- and microscopic analyses of the spatial and temporal distribution of lithics, faunal remains, phytoliths and wood ash, interpreted with the aid of ethnoarchaeological data and comparison to other Palaeolithic sites in the region. Post-depositional disturbance seems to be minimal at Neve David and we therefore suggest that the spatial distribution of the finds mostly represents human use of space. Throughout the thick sequence of occupation episodes, distinct division of space and well-preserved trampled occupation surfaces are generally lacking. We suggest that this pattern represents reduced mobility, as prolonged human activity blurs the primary depositional signal of the activity remains. The density of the finds generally increases in the upper layers of the site. Accordingly, we hypothesize that at the beginning of activity, the duration of occupation was longer and only later in the sequence of events was there an increase in group size. Our findings further highlight the position of the Geometric Kebaran as a pivotal stage in understanding the gap between the preceding highly mobile societies and the succeeding sedentary and demographically-larger Natufian societies.

Effects of computer use on upper limb musculoskeletal disorders and function in academicians

Objectives. This study aimed to investigate the effects of academician’s demographic characteristics and computer usage habits on upper limb musculoskeletal disorders (MSDs) and function. Methods. A cross-sectional observational study was conducted with 100 academicians. Data were collected using questionnaires, which included the patient-rated wrist evaluation questionnaire – Turkish version (PRWE-T), the Cornell musculoskeletal discomfort questionnaire – Turkish version (CMDQ-T), the upper extremity functional index – Turkish version (UEFI-T), demographic characteristics and average daily computer usage time. Results. A low-level significant correlation was found between the age of the individuals and the CMDQ-T forearm (p = 0.044; r = 0.202) and CMDQ-T wrist (p = 0.001; r = 0.337) scores. Women had higher CMDQ-T neck scores and lower UEFI-T scores than men (p < 0.05). Academicians who used computers for 6 h a day or more had higher PRWE-T and CMDQ-T neck, shoulder, upper arm and forearm scores, and had a lower UEFI-T score (p < 0.05). Conclusion. Neck, shoulder, upper arm and forearm symptoms were higher and upper extremity function was impaired in academicians who used computers for 6 h a day or more. Besides, gender and age were associated with upper limb MSDs and function, but occupation duration did not affect those outcomes in academicians.

Feelings of fraud among women in Turkey: Prevalence and demographic risk factors of the Impostor Phenomenon

The Impostor Phenomenon is defined as the inability of individuals to internalize their achievements, believing they are fraudulent. The first aim of this study is to determine the prevalence of the Impostor Phenomenon in women in Turkey. The second aim of the present study is to describe the demographic risk factors of the Impostor Phenomenon. A total of 677 women who work or are undergraduate / graduate students in one of Turkey's four metropolitan cities (Ankara, Bursa, Istanbul, and Izmir) participated in the research. The snowball sampling technique was used for data collection. The ages of the participants ranged from 18 to 65 years (Mage = 31.36, SD = 9.67). The Clance Impostor Phenomenon Scale was used to measure the Impostor Phenomenon, and the Demographic Information Form was used to collect demographic characteristics. The findings showed that 65.73% of the participants had feelings of fraud at least at a moderate level. About 3% of them suffered from the Impostor Phenomenon intensely. In addition, it was found that the Impostor Phenomenon increased as age and duration of occupation decreased. When age was controlled for, it was revealed that low socio-economic status, postgraduate studentship, and postgraduate degree were associated with increased Impostor Phenomenon levels. These findings are discussed in light of the literature on the Impostor Phenomenon and mental health.

Spatiotemporal patterns in habitat use of natal and non-natal adult Atlantic sturgeon in two spawning rivers

BackgroundMonitoring movement across an organism’s ontogeny is often challenging, particularly for long-lived or wide-ranging species. When empirical data are unavailable, general knowledge about species’ ecology may be used to make assumptions about habitat use across space or time. However, inferences about habitat use based on population-level ecology may overlook important eco-evolutionary contributions from individuals with heterogenous ethologies and could diminish the efficacy of conservation and management.MethodsWe analyzed over a decade of acoustic telemetry data to understand individual differences in habitat use of federally endangered adult Atlantic sturgeon (Acipenser o. oxyrinchus) in the Delaware and Hudson rivers during spawning season. In particular, we sought to understand whether sex or natal origin could predict patterns in habitat use, as there is a long-held assumption that adult Atlantic sturgeon seldom stray into non-natal rivers.ResultsIn both rivers, migration timing, spawning habitat occupancy, and maximum upstream migration distance were similar between natal and non-natal individuals. While non-natal individuals represented only 13% of fish detected in the Hudson River, nearly half of all tagged fish detected in the Delaware River were non-natal and generally occupied freshwater habitats longer than natal individuals. In both systems males had more heterogenous patterns of habitat use and longer duration of occupancy than did females.ConclusionsThis study demonstrates the importance of non-natal rivers for fulfilling ontogenetic habitat requirements in Atlantic sturgeon. Our results may also highlight an opportunity to improve conservation and management by extending habitat designations to account for more heterogenous patterns in individual habitat use in non-natal freshwater environments.

A quanta-independent approach for the assessment of strategies to reduce the risk of airborne infection

The Wells-Riley model is extensively used for retrospective and prospective modelling of the risk of airborne transmission of infection in indoor spaces. It is also used when examining the efficacy of various removal and deactivation methods for airborne infectious aerosols in the indoor environment, which is crucial when selecting the most effective infection control technologies. The problem is that the large variation in viral load between individuals makes the Wells-Riley model output very sensitive to the input parameters and may yield a flawed prediction of risk. The absolute infection risk estimated with this model can range from nearly 0 % to 100 % depending on the viral load, even when all other factors, such as removal mechanisms and room geometry, remain unchanged. We therefore propose a novel method that removes this sensitivity to viral load. We define a quanta-independent maximum absolute before-after difference in infection risk that is independent of quanta factors like viral load, physical activity, or the dose-response relationships. The input data needed for a non-steady-state calculation are just the removal rates, room volume, and occupancy duration. Under steady-state conditions the approach provides an elegant solution that is only dependent on removal mechanisms before and after applying infection control measures. We applied this method to compare the impact of relative humidity, ventilation rate and its effectiveness, filtering efficiency, and the use of ultraviolet germicidal irradiation on the infection risk. The results demonstrate that the method provides a comprehensive understanding of the impact of infection control strategies on the risk of airborne infection, enabling rational decisions to be made regarding the most effective strategies in a specific context. The proposed method thus provides a practical tool for mitigation of airborne infection risk.

A cross-sectional study to assess the occupational health hazards among fisherwomen in a metropolitan city.

Research on the working conditions and health hazards of fishing communities in developing countries is scarce. 1) To assess the occupational health hazards among women fish vendors. 2) To understand the morbidity profile in them. 3) To analyze various challenges faced by them at the workplace in this occupation. 4) To suggest various measures including ergonomic solutions that they can take to reduce these health hazards. Community-based observational cross-sectional study. Eight fish markets comprising women fish vendors working for more than one year (age > 30 years) in Mumbai were selected. A cluster sampling method was used. The sample size was 225. The period of the study was 2 years. Chi-square test. The majority of study subjects had diabetes mellitus (24%) and were overweight (54.7%). Of all participants, 55.1% had musculoskeletal pain of which low back pain (69; 30.7%) was most common. There was a significant association between musculoskeletal pain status and mode of carrying boxes, χ2 (1) =56.35 as well as with duration of occupation, χ2 (3) =89.67, P < 0.001. Of all participants, 90.2% got injured of which the majority had incisional wounds (124; 61.1%). Of all participants, 55.1% suffered from skin infections of which the majority (28; 12.4%) had itching and redness of hands and legs. There was a significant association between skin infections and duration of occupation, χ2 (3) =140.53 as well as with the use of gloves (63.2% participants), χ2 (1) =20.395, P < 0.001. Various measures including ergonomic solutions that women fish vendors can take to reduce these health hazards need to be addressed.

Pharmacological Basis of Differences in Dose Response, Dose Equivalence, and Duration of Action of Inhaled Corticosteroids.

Asthma treatment guidelines classify inhaled corticosteroid (ICS) regimens as low, medium, or high dose. However, efficacy and safety are not independently assessed accordingly. Moreover, differences in ICS duration of action are not considered when a dose regimen is selected. We investigated the efficacy and safety implications of these limitations for available ICS molecules. Published pharmacodynamic and pharmacokinetic parameters were used, alongside physiological and pharmacological principles, to estimate the efficacy and safety of available ICS molecules. Extent and duration of glucocorticoid receptor (GR) occupancy in the lung (efficacy) and cortisol suppression (systemic exposure and safety) were estimated. Some ICS regimens (e.g., fluticasone furoate, fluticasone propionate, and ciclesonide) rank high for efficacy but low for systemic exposure, contrary to how ICS dose equivalence is currently viewed. Differences in dose-response relationships for efficacy and systemic exposure were unique for each ICS regimen and reflected in their therapeutic indices. Notably, even low doses of most ICSs can generate high GR occupancy (≥ 90%) across the entire dose interval at steady state, which may explain previously reported difficulties in obtaining dose responses within the clinical dose range and observations that most clinical benefit typically occurs at low doses. The estimated post dose duration of lung GR occupancy for ICS molecules was categorized as 4-6h (short), 14-16h (medium), 25-40h (long), or > 80h (ultra-long), suggesting potentially large differences in anti-inflammatory duration of action. In a real-world clinical setting where there may be poor adherence to prescribed therapy, our findings suggest a significant therapeutic advantage for longer-acting ICS molecules in patients with asthma.

Revaluation of occupancy duration for live load using big data of enterprise credit information

The occupancy duration is an essential variable in establishing the time-varying model of the live load. The manual questioning and inquiries, which are the common survey methods for occupancy duration, suffer from being expensive and time-consuming. This has hindered the updating of the data basis and progress in live load research. This study proposes a novel big data survey method, which utilizes 210 million enterprise credit information to collect occupancy duration samples. Along with the big data survey method, an address-oriented mining method is presented to efficiently extract duration samples of the target type from big data. Based on the actual distribution of the extracted duration data, a more general time-varying model, called the compound renewal process, is suggested to describe the live load. The stochastic harmonic function representation method and probability density evolution method are then adopted to access the maximum load distribution of the live load process. The maximum load distributions of the sustained and combined loads are calculated and compared with previous studies to evaluate the impact of the new survey results. Comparison shows that the occupancy duration of office buildings is significantly shorter, resulting in an increase in the maximum load. The proposed data survey method enables continuous updating of duration samples, and the compound renewal process allows better compatibility for new survey data. The up-to-date duration data and a realistic time-varying model provide new ideas for determining the design live load.

Mobility, site maintenance and archaeological formation processes: An ethnoarchaeological perspective

Mobility is considered to play an important role in the way people use their habitual space. Highly mobile societies present a particular challenge to archaeologists as a direct relation is assumed between the duration of occupation and the intensity of its archaeological signature. Here, we present a cross-cultural, ethnoarchaeological study carried out among three contemporary societies that, while showing different patterns of mobility, all live in humid tropical forests—in Thailand, the Congo Basin, and India—and share many social notions and values. The aim of this study was to observe how differences in patterns of mobility affect the formation of archaeological signatures. Our study demonstrates that when a site is occupied for only a few days to a couple of weeks, activity residues tend to be deposited in situ. This could potentially preserve the original spatial pattern of material distribution that directly reflects the activity areas and people’s use of space. However, when a site is occupied for more than a week or two, maintenance practices such as sweeping begin to take place, which result in almost complete removal of activity residues from their primary location and the formation of waste areas at the edge of the dwelling sites.

Temperature-dependent phototaxis in overwintering adults of the grasshopper Patanga japonica (Orthoptera, Acrididae)

In central Japan, adult Patanga japonica (Bolívar) grasshoppers overwinter as adults while in reproductive diapause. At this local, February nights fall as low as -7°C, whereas days can exceed 16°C. Adults respond to the diel thermal cycle with daily vertical movements out of and back into leaf litter. This paper documents and discusses the significance of this interesting winter behavior. Temperature strongly influenced the daily vertical movements. Time of morning emergence, duration of aboveground occupancy, and number of adults emerging all highly correlated with current and maximum daily temperatures. In January, adults were immobile at &amp;lt; -1°C but could stand up when their body temperatures reached ~3.7°C. In contrast, adults held outdoors in semi-natural conditions emerged from the litter at ~14°C, suggesting threshold temperatures of ~14°C for morning emergence. The numbers of adults emerging or hiding varied over the winter season. Light also influenced movements. Adults held in horizontal transparent tubes, each with half covered with black paper (D-area) and the other half exposed to light (L-area), moved into the L-area during the day and returned to the D-area in the afternoon. In both cases, movement was into a colder microhabitat, implying that the direction of daily movements was possibly via phototaxis, not thermotaxis. Further experiments suggested that increasing temperatures elicited positive phototaxis, and decreasing temperatures elicited negative phototaxis and that the phototaxis was controlled by the direction, magnitude, and absolute range of the temperature change in P. japonica.

Airborne Transmission of SARS-CoV-2: The Contrast between Indoors and Outdoors

COVID-19 is an airborne disease, with the vast majority of infections occurring indoors. In comparison, little transmission occurs outdoors. Here, we investigate the airborne transmission pathways that differentiate the indoors from outdoors and conclude that profound differences exist, which help to explain why SARS-CoV-2 transmission is much more prevalent indoors. Near- and far-field transmission pathways are discussed along with factors that affect infection risk, with aerosol concentration, air entrainment, thermal plumes, and occupancy duration all identified as being influential. In particular, we present the fundamental equations that underpin the Wells–Riley model and show the mathematical relationship between inhaled virus particles and quanta of infection. A simple model is also presented for assessing infection risk in spaces with incomplete air mixing. Transmission risk is assessed in terms of aerosol concentration using simple 1D equations, followed by a description of thermal plume–ceiling interactions. With respect to this, we present new experimental results using Schlieren visualisation and computational fluid dynamics (CFD) based on the Eulerian–Lagrangian approach. Pathways of airborne infection are discussed, with the key differences identified between indoors and outdoors. In particular, the contribution of thermal and exhalation plumes is evaluated, and the presence of a near-field/far-field feedback loop is postulated, which is absent outdoors.

Pollen as food: effects of consumption on tadpole growth, development, and mobility

The structure of many aquatic food webs is influenced by tadpole survivorship and duration of seasonal occupancy, which depend on tadpole diet. Pollen has been occasionally reported to occur in tadpole diets, and the available studies show that tadpoles have a strong preference for this supposedly nutritive resource. Thus, we aimed to test whether a diet composed of pollen from varied plant species would boost tadpole growth, development, and agility/mobility, compared to a regular artificial balanced and nutritive diet. Tadpoles in initial developmental stages 25 and 30 grew more when fed with pollen, compared to artificial food and a mixture of both diets. Those initially in stage 30 advanced more developmental stages during one month when fed exclusively with pollen. Tadpoles fed with pollen moved longer distances in response to an aversive stimulus simulating a predatory attack than tadpoles fed with artificial food or a mixed diet. Our results corroborate the hypotheses of pollen being a very important food source to aquatic consumers such as tadpoles, being likely to influence the structure of aquatic food webs through tadpole nutrition and modulation of growth/development speed, as well as tadpole ability to escape predators.

Chronological Hygiene and Bayesian Modeling of Poverty Point Sites in the Lower Mississippi Valley, circa 4200 to 3200 cal BP

AbstractDevelopments in radiocarbon dating and analysis provide new opportunities to develop high-resolution chronologies to explore changes through time. We explore the temporality of what has been called the Poverty Point culture of the lower Mississippi Valley circa 4200 to 3200 cal BP, especially the chronology of the type site, Poverty Point. Because of its complicated material culture elaboration without evidence of agriculture, Poverty Point has been identified as the political and economic center of a complex archaeological culture. The duration of site occupation and the historical relationship between the type site and those assumed to be contemporary are critical variables for explaining the emergence of complexity at this time. Most interpretations require political or evolutionary processes that accumulate gradually over hundreds of years. Our data show, however, that there is no temporal coherence among so-called Poverty Point culture sites; among such sites, Poverty Point was occupied for a relatively short period, and it is younger than many sites thought to be derived from it. Using explicit radiometric hygiene and Bayesian analyses of dates, we reject the idea of a unified Poverty Point culture and argue instead that the Poverty Point site earthworks developed through rapid, punctuated events occurring circa 3300 to 3200 cal BP.

Idobata-Nagaya: a community housing solution for socially isolated older adults following the great East Japan earthquake.

Following the Great East Japan Earthquake, the living environment of socially isolated older adults has become a pressing concern. In response, Nagaya, a collective housing program, was established in Soma City, Fukushima, Japan to address social isolation among older adults and support their long-term health. This study aimed to identify characteristics of individuals in Nagaya and examine the sustainability of this initiative. We conducted a retrospective analysis of residents who were relocated to Nagaya, emphasizing their characteristics, the continuity of their stay in Nagaya, and their care certification levels, using data up to December 31, 2022. We employed Kaplan-Meier curves to analyze the duration for which residents continued to reside in Nagaya and the time leading up to the requiring care-level certification. Of 65 people who moved to Nagaya after the disaster, 30 people (46.2%) continued to live there, 21 (32.3%) died during their stay, and 14 (21.5%) moved out. The overall duration of occupancy averaged 6.39 years (SD 3.83 years). The proportion of requiring care-level certification occurrences per person-year was 0.0577 for those without care certification and 0.3358 for those with requiring support level at the time of moving in. In summary, Nagaya-style communal housing may offer suitable living environments for older adults with diverse needs during disasters and serve as a valuable tool for developing public policies in aging societies.

Association of selected inflammatory markers and risk factors with pain in patients undergoing cervical or lumbar disc herniation

Introduction&#x0D; Studies have suggested that radicular pain following disc herniation may be associated with local or systemic inflammatory responses produced in the vicinity of the herniated disc rather than compression of the nerve. Present study assessed the association of serum interleukin-6 (IL-6) levels, high-sensitivity C-reactive protein (hs-CRP) and related risk factors in patients undergoing discectomy following cervical disc herniation (CDH) or lumbar disc herniation (LDH).&#x0D; Methods&#x0D; Study recruited 77 patients undergoing discectomy for LDH and CDH. An interviewer administered questionnaire was used to obtain sociodemographic, behavioral and occupational data. IL-6 and hs-CRP levels were measured in each individual. IL-6 was analyzed by ELISA method and hs-CRP was determined using auto analyzer. Results were analyzed by using SPSS version 25.0.&#x0D; &#x0D; Results&#x0D; Significant correlation was not found with serum IL-6 and hs-CRP levels (r=0.02, p˃0.05) for acute and chronic CDH and LDH. Patients with chronic neck or back pain showed significantly (p=0.043) higher IL-6 level compared to patients with acute neck or back pain. Serum hs-CRP level was significantly higher (p=0.048) in patients with acute neck or back pain compared to patients with chronic neck or back pain. Significant association was not observed between; level of physically demanding nature of occupation (p=0.542), duration of occupation (p=0.446), type of exercise (p=0.371), type of sports (p=0.339) and CDH or LDH.&#x0D; Conclusion&#x0D; Though significant correlation was not observed between inflammatory markers IL-6, hs-CRP and CDH or LDH. The mean IL-6 was higher in chronic back pain and neck pain patients with LDH and CDH whereas mean hs-CRP mean was higher in acute back pain and neck pain patients. Significant association was not reported between selected known risk factors (behavioral, occupational) and CDH or LDH.

New Tocilizumab (TCZ) Dosing Guidance for T-Cell Engaging Bispecific Antibody-Related Cytokine Release Syndrome (CRS) in Patients (pts) with Relapsed/Refractory (R/R) B-Cell Non-Hodgkin Lymphoma (B-NHL): Insights from Pooled Clinical Trial Safety Experience and Quantitative Clinical Pharmacology (qCP) Analyses

Background: Mosunetuzumab (Mosun), approved for treatment of pts with R/R follicular lymphoma (FL) and ≥2 prior therapies, and glofitamab (Glofit), approved for treatment of pts with R/R diffuse large B-cell lymphoma, or large B-cell lymphoma arising from FL, and ≥2 prior therapies, are CD20xCD3 T-cell engaging bispecific antibodies that redirect T cells to eliminate B cells. CRS is a common on-target adverse event observed with bispecific antibodies and associated with exposure. TCZ, a humanized anti-interleukin-6 (IL-6) receptor, is often used for CRS management. TCZ dosing recommendations derived from CAR T-cell studies (Le et al. Oncologist 2018) may not be optimal for bispecific antibody-treated pts. Using TCZ clinical usage patterns in Mosun- or Glofit-treated pts with R/R B-NHL, qCP, and cytokine analyses, we explored a new TCZ dosing regimen for CRS management (for pts &amp;gt;30 kg body weight). Methods: Pooled safety data from seven Phase I/II studies evaluating Mosun or Glofit in pts with R/R B-NHL were analyzed. CRS was graded using ASTCT criteria (Lee et al. Biol Blood Marrow Transplant 2019). Modeling was used to predict TCZ concentrations (conc) and soluble IL-6 receptor (s-IL6R) occupancy over time, following administration of different TCZ dosing regimens in a subset of pts. Downstream cytokine pharmacodynamic responses (IL-6 and C-reactive protein [CRP]) were evaluated graphically post-TCZ dosing. Results: Data from 733 Mosun- and 772 Glofit-treated pts across different Mosun/Glofit dose levels were analyzed; of these, 232 (31.7%) and 427 (55.3%) pts, respectively, had ≥1 CRS event, and 36/232 (15.5%) and 140/427 (32.8%) pts received TCZ for CRS management. CRS events were mainly Grade 1/2 and occurred during the first treatment cycle. Most pts who received TCZ for CRS received ≤2 doses of TCZ overall (Mosun: 94.4%; Glofit: 84.2%) ( Table), and 1 dose of TCZ for the management of a single CRS event (Mosun: 91.7%; Glofit: 84.9%). CRS resolution was achieved within 3 days of TCZ administration in 75.0% and 66.9% of Mosun- and Glofit-treated pts, respectively. By then, a reduction in IL-6 and CRP levels was also observed. In a prior pharmacokinetic (PK) analysis of TCZ in pts with CAR T-cell-associated CRS, predicted TCZ conc after administration of 4 intravenous (IV) TCZ doses of 8 mg/kg every 8 hours (q8h) was generally below 649 μg/mL, the observed maximum conc in healthy volunteers and “safety threshold” used by the FDA (Le et al. Oncologist 2018). qCP analyses of TCZ PK and s-IL6R data from 67 pts who received TCZ for CRS management following treatment with Mosun or Glofit indicated that this TCZ regimen may exceed the safety threshold, in part because maximum TCZ conc is one-third lower in pts with CAR T-cell-induced CRS vs bispecific antibody-induced CRS. In addition, typical bispecific antibody regimens involve multiple doses compared with a single CAR T-cell infusion, with the potential for multiple CRS events requiring TCZ treatment; therefore, TCZ accumulation must be considered. qCP simulations predicted that for 1 x 8 mg/kg dose, median duration of &amp;gt;90% s-IL6R saturation was 28 (range: 14-28) days ( Table). Furthermore, simulations indicated that ≤2 consecutive TCZ doses q8h per CRS event and a maximum of 3 TCZ doses within a 6-week time period maintain the TCZ conc below the FDA safety threshold, while ensuring sustained s-IL6R occupancy ( Table). Conclusions: qCP results and clinical experience in Mosun and Glofit studies support a TCZ dosing regimen of ≤2 IV doses of 8 mg/kg per CRS event administered q8h, not exceeding a total of 3 doses within a 6-week period. Further improvement in CRS management and symptom resolution with additional TCZ doses is unlikely given the predicted duration of s-IL6R occupancy and observed rapid decline in systemic inflammatory markers post dosing. This proposed TCZ dosing regimen reflects TCZ usage patterns in clinical trials evaluating Mosun and Glofit, and is included in their Summaries of Product Characteristics. In patients with R/R B-NHL receiving bispecific antibody treatment, TCZ is generally suitable for management of acute CRS, and balances risk-benefit for potential scenarios involving multiple TCZ administrations for pts with CRS recurrence. This recommendation considers TCZ safety factors, the unique PK properties of TCZ in this setting and the expected duration of activity based on pharmacological modeling of target binding (s-IL6R occupancy).