Unknown Factors Research Articles

A data-driven optimal time-delayed control approach and its application to aerial manipulators

In this paper, a data-driven optimal time-delayed control (TDC) approach is developed for Euler–Lagrange systems and applied to an aerial manipulator. The proposed approach is able to deal with the nonlinearity and handle unmodelled dynamics, model uncertainties and unknown disturbances in Euler–Lagrange systems. The time-delayed estimation employed in the proposed approach uses the measurement information at the last time instant to approximately estimate all the unknown factors at the current time instant. A constant gain matrix is the main design parameter and influences both the closed-loop stability and the tracking performance. Currently, this constant gain matrix is either calculated by using the system model based on a stability condition or obtained by trial and error, both of which are rather time-consuming in practice. The data-driven TDC approach developed in this paper can find the constant gain matrix directly from the input and output data without any knowledge of the inertia matrix. To achieve optimal control performance, an LQR term is integrated in the data-driven design. The input-to-state stability of the closed-loop system is proven. The proposed approach is characterized by easy implementation and low computational efforts. The application to the aerial manipulator and the experiment results with a hexacopter demonstrate the effectiveness of the proposed approach.

Impact of the COVID-19 pandemic on breast cancer incidence and tumor stage in the Netherlands and Norway: A population-based study

BackgroundComparing the impact of the COVID-19 pandemic on the incidence of newly diagnosed breast tumors and their tumor stage between the Netherlands and Norway will help us understand the effect of differences in governmental and social reactions towards the pandemic. MethodsWomen newly diagnosed with breast cancer in 2017–2021 were selected from the Netherlands Cancer Registry and the Cancer Registry of Norway. The crude breast cancer incidence rate (tumors per 100,000 women) during the first (March-September 2020), second (October 2020-April 2021), and Delta COVID-19 wave (May-December 2021) was compared with the incidence rate in the corresponding periods in 2017, 2018, and 2019. Incidence rates were stratified by age group, method of detection, and clinical tumor stage. ResultsDuring the first wave breast cancer incidence declined to a larger extent in the Netherlands than in Norway (27.7% vs. 17.2% decrease, respectively). In both countries, incidence decreased in women eligible for screening. In the Netherlands, incidence also decreased in women not eligible for screening. During the second wave an increase in the incidence of stage IV tumors in women aged 50–69 years was seen in the Netherlands. During the Delta wave an increase in overall incidence and incidence of stage I tumors was seen in Norway. ConclusionAlterations in breast cancer incidence and tumor stage seem related to a combined effect of the suspension of the screening program, health care avoidance due to the severity of the pandemic, and other unknown factors.

Real-World Outcomes with Chimeric Antigen Receptor T Cell Therapies in Large B Cell Lymphoma: A Systematic Review and Meta-Analysis

Chimeric antigen receptor T cell (CAR-T) therapies, including axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel), are innovative treatments for patients with relapsed or refractory (r/r) large B cell lymphoma (LBCL). Following initial regulatory approvals, real-world evidence (RWE) of clinical outcomes with these therapies has been accumulating rapidly. Notably, several large registry studies have been published recently. Here we comprehensively describe clinical outcomes with approved CAR-T therapies in patients with r/r LBCL using available RWE. We systematically searched Embase, MEDLINE, and 15 conference proceedings to identify studies published between 2017 and July 2022 that included ≥10 patients with r/r LBCL treated with commercially available CAR-T therapies. Eligible study designs were retrospective or prospective observational studies. Key outcomes of interest were objective response rate (ORR), complete response (CR) rate, overall survival (OS), progression-free survival (PFS), cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). Random-effects meta-analyses were used to compare real-world outcomes with those of pivotal clinical trials and to compare clinical outcomes associated with axi-cel and tisa-cel. Study cohort mapping was conducted to avoid including patients more than once. Of 76 cohorts we identified, 46 reported patients treated specifically with either axi-cel or tisa-cel, with 39 cohorts (n = 2754 patients) including axi-cel and 20 (n = 1649) including tisa-cel. No studies of liso-cel that met the inclusion criteria were identified during the search period. One-half of the tisa-cel cohorts were European, compared with 33% of the axi-cel cohorts. Among studies with available data, axi-cel had a significantly shorter median time from apheresis to CAR-T infusion than tisa-cel. Despite including broader patient populations, real-world effectiveness and safety of both axi-cel and tisa-cel were consistent with data from the pivotal clinical trials. Comparative meta-analysis of axi-cel versus tisa-cel demonstrated adjusted hazard ratios for OS and PFS of .60 (95% confidence interval [CI], .47 to .77) and .67 (95% CI, .57 to .78), respectively, both in favor of axi-cel. Odds ratios (ORs) for ORR and CR rate, both favoring axi-cel over tisa-cel, were 2.05 (95% CI, 1.76 to 2.40) and 1.70 (95% CI, 1.46 to 1.96), respectively. The probability of grade ≥3 CRS was comparable with axi-cel and tisa-cel, whereas axi-cel was associated with a higher incidence of grade ≥3 ICANS (OR, 3.95; 95% CI, 3.05 to 5.11). Our meta-analysis indicates that CAR-T therapies have manageable safety profiles and are effective in a wide range of patients with r/r LBCL, and that axi-cel is associated with improved OS and PFS and increased risk of grade ≥3 ICANS compared with tisa-cel. Limitations of this study include nonrandomized treatments, potential unknown prognostic factors, and the lack of available real-world data for liso-cel.

Biot's theory-based dynamic equation modeling using a machine learning auxiliary approach

Abstract Characterizing seismic wave propagation in a fluid-saturated porous media well enhances the precision of interpreting seismic data, bringing benefits to understanding reservoir properties better. Some important indicators, including wave dispersion and attenuation, along with the wavefield, are widely used for interpreting the reservoir, and they can be obtained from a rock physics model. In existing models, some of them are limited in scope due to their complexity, for example, numerical solutions are difficult or costly. In view of this, this study proposes an approach of establishing equivalent dynamic equations of existing models. First, the framework of the equivalent model is derived based on Biot's theory, while the elastic coefficients are set as unknown factors. The next step is to use deep neural networks (DNNs) to predict these coefficients, and surrogate models of unknowns are established after training DNNs. The training data is naturally generated from the original model. The simplicity of the equation forms, compared to the original complex model and some other equivalents such as the viscoelastic model, enables the framework to perform wavefield simulation easier. Numerical examples show that the established equivalent model can not only predict similar dispersion and attenuation, but also obtain wavefields with small differences. This also indicates that it may be sufficient to establish an equivalent model only according to dispersion and attenuation, and the cost of generating such data is very small compared to simulating the wavefield. Therefore, the proposed approach is expected to effectively improve the computational difficulty of some existing models.

Impact of the COVID-19 pandemic on the mortality among patients with colorectal cancer in Hiroshima, Japan: A large cancer registry study.

This retrospective cohort study aimed to evaluate the impact of the COVID-19 pandemic on colorectal cancer care and mortality using a large cancer registry in Hiroshima Prefecture, Japan. The study aimed to estimate the all-cause mortality rates within 1 year of diagnosis among colorectal cancer patients diagnosed during the pandemic period (2020 and 2021) compared to those diagnosed during the pre-pandemic period (2018 and 2019). The day of diagnosis was set as Day 0 and Cox regression models were utilized to estimate crude hazard ratios (HRs) and adjusted HRs, accounting for age, sex, cancer stage, and treatment status. Two sensitivity analyses of overall survival were performed with different cutoffs of the pre-pandemic/pandemic periods and year-to-year comparisons. Subgroup analyses were performed using likelihood ratio tests. A total of 15,085 colorectal cancer patients were included, with 6499 eligible for follow-up. A median age of included patients was 72 years old, of which 59% were male. The distribution of cancer stages showed little variation between the pre-pandemic and pandemic periods. With a median follow-up of 177 days, the number of events was 316/3111 (173 events per 1000 person-years [E/1000PY], 95% confidence interval [CI]: 154-192 E/1000PY) in the pre-pandemic period, and 326/2746 (245 E/1000PY, 95% CI: 220-274 E/1000PY) in the pandemic period (crude HR: 1.42, 95% CI: 1.22-1.66; adjusted HR: 1.25, 95% CI: 1.07-1.46). The two sensitivity analyses and subgroup analyses consistently supported these findings. The study revealed an increased colorectal cancer mortality during the pandemic period, suggesting a continuous impact of the COVID-19 pandemic on the known and unknown risk factors for colorectal cancer for several years. Further studies are necessary to mitigate the adverse effects on patient outcomes.

Safety, health, and environmental risk assessment of the aromatic outlet of Imam Khomeini Petrochemical Company using LOPA and fuzzy-LOPA and pollutants and control actions using the Bow-tie method.

Today, with the development of the industry, the occurrence of accidents caused by the release and explosion of chemical and toxic substances in industrial units has increased, and these accidents sometimes cause irreparable damage to human life and the environment. According to a study by the American Petroleum Institute, of the recent major accidents in the last 30 years, 44% are related to machinery failure and 12% are caused by unknown factors and lack of information. Therefore, equipment risk control is aimed at preventing large and dangerous accident. The present study, the performance of LOPA and fuzzy-LOPA methods was compared toward the risk assessment of Imam Khomeini Petrochemical Company under certainty and uncertainty of data. This comparison was done in order to a conceptual method with high certainty to assess high-level hazards leading to health and safety risks and environmental pollution. First, the health, safety hazards and environmental aspects were identified via the HAZOP method. Then, a risk assessment was performed using the LOPA method. The fuzzification, severity, and likelihood of each risk were considered as an input variable and risk probability as an output variable. Finally, was the methods used in our analysis were compared and the Bow-tie software was used to draw a Bow-tie diagram to control and reduce the risks. As a result, a total of 50 safety and health hazards and 37 environmental aspects were identified in the aromatic outlet of the studied company using the HAZOP method. The most critical risks identified were operational activities in feed and product tanks; flammable materials pumping; blocking the flare path; and releasing H2S gas. The results showed that the production of air pollutants in the power supply unit, disposal of waste from reactor tanks, disposal of waste from condensate tanks, and fire and explosion of the reactor are high-level environmental risks. In the conditions of uncertainty or the absence of information related to the probability and severity of the risk scenario, among the mentioned methods. The result showed that errors in the risk assessment were reduced to an acceptable extent by using Fuzzy LOPA method.

Intervention Research in Health Promotion: Policy Issues, the Example of the Ten-Year Cancer Strategy in France

Abstract Prevention research covers a wide range of studies, including the identification of unknown risk factors for certain cancers, or health promotion with approaches by population, by living environment or by territory. This research focuses in particular on identified carcinogenic factors (e.g. tobacco, alcohol, food, certain pesticides) but also on the causes of the prevalence of these factors in certain populations. In addition, surveys on perceptions of cancer and cancer risk factors - such as the 2021 French Cancer Barometer - are needed. They provide a better understanding of behaviour in order to propose targeted and effective interventions. In this context, the PHIR makes it possible to respond to these challenges. In 2010, the French National Cancer Institute was a pioneer in the development of PHIR in France and decided in 2021 to make it one of the spearheads of its ten-year strategy. This presentation aims to report on this policy of developing PHIR as a relevant tool for thinking about health promotion policies and actions, particularly on nutrition, with a focus on health inequalities and on certain populations (young people, vulnerable populations). The presentation will address three challenges for the implementation of this research policy: 1/ the development of the French scientific community in order to be able to respond to priority issues; 2/ the support of research on this topic and the animation of this community; 3/ the use of PHIR as a tool to define health promotion policies and actions. The first part will focus on identifying the modalities of implementation of the PHIR in the framework of a national policy of prevention and health promotion. The second part will focus on the challenges of its deployment among the French scientific community.

Regulation of axon pathfinding by astroglia across genetic model organisms

Glia and neurons are intimately associated throughout bilaterian nervous systems, and were early proposed to interact for patterning circuit assembly. The investigations of circuit formation progressed from early hypotheses of intermediate guideposts and a “glia blueprint”, to recent genetic and cell manipulations, and visualizations in vivo. An array of molecular factors are implicated in axon pathfinding but their number appears small relatively to circuit complexity. Comprehending this circuit complexity requires to identify unknown factors and dissect molecular topographies. Glia contribute to both aspects and certain studies provide molecular and functional insights into these contributions. Here, I survey glial roles in guiding axon navigation in vivo, emphasizing analogies, differences and open questions across major genetic models. I highlight studies pioneering the topic, and dissect recent findings that further advance our current molecular understanding. Circuits of the vertebrate forebrain, visual system and neural tube in zebrafish, mouse and chick, the Drosophila ventral cord and the C. elegans brain-like neuropil emerge as major contexts to study glial cell functions in axon navigation. I present astroglial cell types in these models, and their molecular and cellular interactions that drive axon guidance. I underline shared principles across models, conceptual or technical complications, and open questions that await investigation. Glia of the radial-astrocyte lineage, emerge as regulators of axon pathfinding, often employing common molecular factors across models. Yet this survey also highlights different involvements of glia in embryonic navigation or pioneer axon pathfinding, and unknowns in the molecular underpinnings of glial cell functions. Future cellular and molecular investigations should complete the comprehensive view of glial roles in circuit assembly.

Accounting for changes in income inequality in China, 2002–2018: evidence from household survey data

This paper examines causes behind recent changes in income inequality in China, especially its moderation since 2008, using household survey data and decomposition analyses. It is found that, by income sources, contributors to the moderation in inequality were wage income, pension, and other transfers, offset somewhat by the inequality‐increasing effect of changes in net farm and nonfarm business incomes, net asset income, imputed rent, and personal income tax and social security contribution. By household characteristics, contributors to inequality moderation were a narrowing in the urban–rural income gap, rural–urban migration, and a decline in regional income disparity, offset by widening inter‐industry earning differentials, a rise in the education premium, and changes in some unknown factors. These results are likely an outcome of some fundamental drivers working together, including processes of catch‐up growth and structural transformation, market‐driven forces including technological progress and globalisation, government policy actions, and remaining market distortions.

Minimization in randomized clinical trials.

In randomized trials, comparability of the treatment groups is ensured through allocation of treatments using a mechanism that involves some random element, thus controlling for confounding of the treatment effect. Completely random allocation ensures comparability between the treatment groups for all known and unknown prognostic factors. For a specific trial, however, imbalances in prognostic factors among the treatment groups may occur. Although accidental bias can be avoided in the presence of such imbalances by stratifying the analysis, most trialists, regulatory agencies, and other stakeholders prefer a balanced distribution of prognostic factors across the treatment groups. Some procedures attempt to achieve balance in baseline covariates, by stratifying the allocation for these covariates, or by dynamically adapting the allocation using covariate information during the trial (covariate-adaptive procedures). In this Tutorial, the performance of minimization, a popular covariate-adaptive procedure, is compared with two other commonly used procedures, completely random allocation and stratified blocked designs. Using individual patient data of 2 clinical trials (in advanced ovarian cancer and age-related macular degeneration), the procedures are compared in terms of operating characteristics (using asymptotic and randomization tests), predictability of treatment allocation, and achieved balance. Fifty actual trials of various sizes that applied minimization for treatment allocation are used to investigate the achieved balance. Implementation issues of minimization are described. Minimization procedures are useful in all trials but especially when (1) many major prognostic factors are known, (2) many centers of different sizes accrue patients, or (3) the trial sample size is moderate.

Electric vehicle fire risk assessment framework using Fault Tree Analysis.

In the near future, the rapid adoption of electric vehicles is inevitable, driven by environmental concerns and climate change awareness. However, this progressive trend also brings forth safety concerns and hazards, notably regarding the risk of EV fires, which have garnered significant media attention. This necessitates the need to study for comprehensive fire risk assessment strategies aimed at preventing and mitigating such incidents. This study presents a framework for assessing fire risks in EVs using Fault Tree Analysis (FTA). By integrating disparate data sources into a unified dataset, the proposed methodology offers a holistic approach to understanding potential hazards. The study embarked on a comprehensive exploration of EV fire causes through qualitative FTA. Through this approach, the work discerned five major causes: human factors, vehicle factors, management factors, external factors, and unknown factors. Using a meticulous weighted average approach, the annual EV fire frequency for each country was deduced, revealing an average annual EV fire rate of 2.44 × 10 -4 fires per registered EV. This metric provides a significant benchmark, reflecting both the probability and inherent risk of such incidents. However, uncertainties in data quality and reporting discrepancies highlight the imperative of continued research. As EV adoption surges, this study underscores the importance of comprehensive, data-driven insights for proactive risk management, emphasizing the necessity for vigilant and adaptive strategies. The findings emphasize the pivotal role of this assessment in shaping response strategies, particularly for first responders dealing with EV fires. In essence, this research not only elevates the understanding of EV fire risks but also offer a foundation for future safety measures and policies in the domain.

Impact of Basic Needs Fulfillment on the Health, Well-being, and Academic Engagement of Occupational Therapy Students

The basic needs of students may serve as unknown factors in academic engagement and well-being. Challenges in meeting these needs disproportionately impact underrepresented minority and first-generation students. The purpose of this pilot study was to explore the perceived presence and impact of basic needs on health, well-being, and academic engagement in occupational therapy students. A 43-item survey was distributed to 231 students and focused on questions addressing basic needs in physiology, safety, and belonging. Respondents reported worry over or the need to work to pay bills, no support from family/friends, and limited access to food in the past 30 days and related this to feeling stressed, not being able to do homework, not participating in class, and loss of leisure time. Ninety-four percent used student health services frequently. Recommendations to address gaps in basic needs include flexible policies, inclusive learning environments, supportive and intentional actions, and providing resources.

A human pilot study on positive electrostatic charge effects in solid tumors of the late-stage metastatic patients.

Correlative interactions between electrical charges and cancer cells involve important unknown factors in cancer diagnosis and treatment. We previously reported the intrinsic suppressive effects of pure positive electrostatic charges (PEC) on the proliferation and metabolism of invasive cancer cells without any effect on normal cells in cell lines and animal models. The proposed mechanism was the suppression of pro-caspases 3 and 9 with an increase in Bax/Bcl2 ratio in exposed malignant cells and perturbation induced in the KRAS pathway of malignant cells by electrostatic charges due to the phosphate molecule electrostatic charge as the trigger of the pathway. This study aimed to examine PECs as a complementary treatment for patients with different types of solid metastatic tumors, who showed resistance to chemotherapy and radiotherapy. In this study, solid metastatic tumors of the end-stage patients (n = 41) with various types of cancers were locally exposed to PEC for at least one course of 12 days. The patient's signs and symptoms, the changes in their tumor size, and serum markers were followed up from 30 days before positive electrostatic charge treating (PECT) until 6 months after the study. Entirely, 36 patients completed the related follow-ups. Significant reduction in tumor sizes and cancer-associated enzymes as well as improvement in cancer-related signs and symptoms and patients' lifestyles, without any side effects on other tissues or metabolisms of the body, were observed in more than 80% of the candidates. PECT induced significant cancer remission in combination with other therapies. Therefore, this non-ionizing radiation would be a beneficial complementary therapy, with no observable side effects of ionizing radiotherapy, such as post-radiation inflammation.

Functional Impairment, Attachment, and Affective Temperaments in Euthymic Patients with Bipolar Disorder.

Functional impairment in euthymic patients with bipolar disorder is a compelling issue, and revealing unknown related factors with functional impairment is a substantial topic. We aimed to assess the effects of clinical factors, affective temperaments, and attachment on overall functioning in euthymic patients with bipolar disorder. Sixty-three patients with bipolar disorder and 61 healthy controls participated in this study. The assessment involved Hamilton Depression Rating Scale; Young Mania Rating Scale; Relationship Scales Questionnaire; Temperament Evaluation of Memphis, Pisa, Paris, and San Diego; and Functioning Assessment Short Test. Secure attachment scores were significantly higher in the control group than in the bipolar disorder group. Depressive, anxious, and cyclothymic temperament scores were significantly higher in the bipolar disorder group. In the bipolar disordergroup higher occupational, cognitive, autonomy, interpersonal relationships, and leisure subdomain and overall functional impairment scores were found than in the healthy control group. Secure attachment scores were significantly and negatively correlated with anxious and depressive temperaments. Secure attachment scores were positively and significantly correlated with hyperthymic temperament scores. Years of education; subclinical depressive symptoms; secure attachment; and cyclothymic, irritable, depressive, hyperthymic, and anxious temperaments were all significantly correlated with the overall functional impairment in the patient group. The cyclothymic and anxious temperament positively predicted the overall functional impairment in the bipolar group, while the secure attachment negatively predicted the overall functional impairment in the regression analysis. The results suggest that, when following up the patients with bipolar disorder in relation to functional impairment, secure attachment, cyclothymic, and anxious temperaments should be taken into consideration.

Police Realistic Tactical Training Is Not Risk-Free: Stress-Induced Wide-QRS Paroxysmal Tachyarrhythmia in a Healthy Police Officer and Professional Athlete

The reported case, a spin-off of a wider ongoing national study investigating the individual stress reactions of police officers during realistic police tactical training, highlights the eventuality that stress-induced paroxysmal arrhythmias might occur and remain undetected without ECG monitoring as a standard practice. The ECG of a 41-year-old frontline police officer (and professional athlete of the State Police’s rugby team) was monitored with a wireless, textile-based, wearable device during stressful scenarios implying the use of force. ECG data were processed with the Kubios software to assess training-induced time-varying changes of heart rate variability parameters and of the parasympathetic, sympathetic, and stress indices. Multiparametric analysis of the heart rate variability quantified remarkable stress-induced increment of vagal withdrawal and of sympathetic dominance, with exceptionally high-stress index and sudden occurrence of a wide-QRS paroxysmal tachyarrhythmia (240 bpm) with concomitant operational failure. Subsequent exhaustive mandatory clinical assessment excluded any structural and arrhythmogenic cardiac abnormality. Although exceptional and to the best of our knowledge so far unique, the recording of a stress-induced paroxysmal wide-QRS arrhythmia occurring during realistic tactical training in a healthy police officer and highly fit athlete is worth to be shared as a caveat about the potential risk if eventually occurring in officers with unknown cardiovascular risk factors (e.g., for ischemic heart disease). Moreover, the demonstration that such a high level of stress may occur even in an experienced, healthy, and highly fit officer altering the physiologic dynamicity of brain–heart interaction with a negative consequence on the operational outcome strongly suggests that individual emotional reactions induced by stressful duty events must be safely experienced and assessed with realistic training, to adopt preventive coping strategies, to improve police officers’ efficiency in front of threats, and to lower the risk of inappropriate use of force with dramatic consequences on the street.

Nonlinear low-velocity impact of magneto-electro-elastic plates with initial geometric imperfection

Magneto-electro-elastic (MEE) materials are widely used in the aviation and spaceflight area, attributed to magneto-electric coupling effect of MEE materials which can achieve mutual energy conversion in complex physical fields. This article takes the imperfect MEE plate as the research object to explore the nonlinear low-velocity behaviors, and the influence of multiple physical fields such as electric, magnetic and temperature fields are taken into account. Based on Maxwell's equations and first-order shear deformation theory (FSDT), the constitutive equation of MEE plate is obtained, and the nonlinear motion equations are derived using the Euler-Lagrange principle. Subsequently, with the aid of the Galerkin method, the ordinary differential equations are obtained by discretizing the partial differential equations. Then the low-velocity impact problem is solved using the Runge-Kutta method. Finally, the impacts of unknown factors upon the dynamic behaviors of the MEE plate are illustrated particularly. It can be found that the magnetic and electric potentials have opposite effects on the impact displacement of the plate, and the MEE plate with the lowest volume fraction of BaTiO3 has the smallest center displacement and the shortest contact time, but has the maximum contact force.

Diurnal predators of restocked lab-reared and wild Diadema antillarum near artificial reefs in Saba.

The long-spined sea urchin Diadema antillarum controls reef dynamics by grazing on algae and increasing coral recruitment. Populations of Diadema never recovered after a mass-die off in 1983 and 1984, and numbers were further reduced by a more recent die-off in 2022. To restore grazing pressure and thereby the resilience of Caribbean coral reefs, multiple Diadema restocking efforts have been performed. Although results vary, relatively low retention is one of the reasons restocking is not considered more often. If causes for the low retention can be identified, suitable measures may be able to increase restocking success. In this study, we monitored restocked lab-reared and wild juvenile Diadema on artificial reefs around Saba, Caribbean Netherlands. To assess the retention of Diadema over time, we conducted diver surveys and used underwater photo time lapse during daylight. Retention of uncaged lab-reared and wild Diadema decreased steadily with less than 30% surviving after 10 days. In total, 138 predator-prey interactions were recorded, of which 99% involved the queen triggerfish Balistes vetula, although other potential predators were present in the area. None of the recorded predator-prey interactions was successful, which suggests that artificial reefs with incorporated shelters may be suitable for juveniles as daytime refuge. However, Diadema that were more often attacked during the day were more likely to be absent the next morning. Because queen triggerfish often visited the experimental site in the first or last hour of daylight, it could be that they were more successful in their attacks when it was too dark to see anything on the photos and when Diadema came out to feed or to look for better shelter opportunities. If Diadema migrated off the artificial reef, they were probably predated during the process, because no Diadema were found on surrounding reefs. Wild Diadema were attacked significantly more often than lab-reared Diadema, possibly because the wild urchins were larger, but this did not significantly affect retention. Future restocking should be performed on natural or artificial reefs with deeper shelters, so Diadema can retract farther into their crevice, and should include night-time monitoring to identify the remaining unknown factors that cause low retention, including migration and nocturnal predation. This knowledge is urgently needed to coral reef managers so they can increase Diadema restocking success by selecting reefs with a lower predator density, protect urchins during an acclimatization period and/or conduct temporary predator control measures.

Stigmatized attitudes of medical staff toward people who use drugs and their determinants in Japanese medical facilities specialized in addiction treatment.

Stigma within healthcare settings significantly impact the lives of people who use drugs (PWUD). Given the lack of quantitative data on stigma toward PWUD in healthcare settings and the unknown factors that contribute to it in the Japanese context, this study aimed to investigate the current status of stigma toward PWUD and its determinants. We conducted a survey in five specialized addiction medical facilities across three prefectures in Japan. The survey included questions related to stigmatizing attitudes toward PWUD, knowledge about illicit drug use, and personal and professional interactions with PWUD. A substantial portion of respondents rejected the notion that drug addiction can be overcome through sheer willpower or attributed it solely to moral failings. However, the majority still considered them untrustworthy and viewing drug use as unacceptable and incomprehensible. Many respondents perceived PWUD as dangerous, despite the limited occurrence of hostile behavior from PWUD in clinical practice. A considerable proportion of respondents did not seek support for their own or their relatives' drug-related issues, and less than half had collaborated with recovered PWUD, which serves as potential indicators of reduced stigma. While healthcare professionals recognized that involving law enforcement does not contribute to the recovery of PWUD, a considerable number still believed it was necessary to report them to the authorities. Healthcare professionals in specialized addiction medical facilities demonstrate strong stigmatizing attitudes toward PWUD. Comprehensive educational programs and large-scale awareness campaigns are necessary to address and mitigate stigma in this context.

A Study on Prognostic Factors in Management of Breast Carcinoma in A Tertiary Care Hospital

Breast cancer is the most common malignant tumor and leading cause of death in women worldwide. It accounts for 15% of all cancer deaths According to World Health Organisation (WHO), approximately 70% of breast malignancies occur in women with unknown risk factorsThe prognostic factor can be defined as a measurable variable which correlates with natural history of the disease. The most significant factor which influences prognosis in breast cancer is axillary lymph node involvement, which is usually assessed at time of surgery using sentinel lymph node biopsy or axillary lymph node dissection. The number of lymph nodal involvement is also significant. Involvement of 1-3 lymph nodes carry better prognosis than 4-9 and more than 9 lymph nodes involvement. Size of the tumour has long been recognized as a prognostic factor and as predictor of axillary node status, with larger tumours being associated with a bad prognosis and an increased incidence of nodal metastasis. This study is conducted in Department of General Surgery, SVRRGGH, Sri Venkateswara Medical College, Tirupati for a period of more than one and half year after getting approval from Institutional Ethical Committee on March 2021. A prospective study of 50 patients who fulfilled Inclusion Criteria is taken into consideration to know how prognostic factors like tumor size & grade, axillary lymphnode involvement are influencing the prognosis and management of breast carcinoma. Patients who took part in the study were from 28-68 years of age. Majority of people were in the age group of 46-55 years (38%). Increasing age, involvement of axillary lymph nodes, tumors with larger size and higher grade, and lymphovascular invasions are all associated with worse prognosis Keywords: Estrogen Receptor, Progesterone Receptor, Locally Advanced Breast Carcinoma

Emerging roles for diguanylate cyclase during the evolution of soma in dictyostelia

BackgroundCyclic di-guanylate (c-di-GMP), synthesized by diguanylate cyclase, is a major second messenger in prokaryotes, where it triggers biofilm formation. The dictyostelid social amoebas acquired diguanylate cyclase (dgcA) by horizontal gene transfer. Dictyostelium discoideum (Ddis) in taxon group 4 uses c-di-GMP as a secreted signal to induce differentiation of stalk cells, the ancestral somatic cell type that supports the propagating spores. We here investigated how this role for c-di-GMP evolved in Dictyostelia by exploring dgcA function in the group 2 species Polysphondylium pallidum (Ppal) and in Polysphondylium violaceum (Pvio), which resides in a small sister clade to group 4.ResultsSimilar to Ddis, dgcA is upregulated after aggregation in Ppal and Pvio and predominantly expressed in the anterior region and stalks of emerging fruiting bodies. DgcA null mutants in Ppal and Pvio made fruiting bodies with very long and thin stalks and only few spores and showed delayed aggregation and larger aggregates, respectively. Ddis dgcAˉ cells cannot form stalks at all, but showed no aggregation defects. The long, thin stalks of Ppal and Pvio dgcAˉ mutants were also observed in acaAˉ mutants in these species. AcaA encodes adenylate cyclase A, which mediates the effects of c-di-GMP on stalk induction in Ddis. Other factors that promote stalk formation in Ddis are DIF-1, produced by the polyketide synthase StlB, low ammonia, facilitated by the ammonia transporter AmtC, and high oxygen, detected by the oxygen sensor PhyA (prolyl 4-hydroxylase). We deleted the single stlB, amtC and phyA genes in Pvio wild-type and dgcAˉ cells. Neither of these interventions affected stalk formation in Pvio wild-type and not or very mildly exacerbated the long thin stalk phenotype of Pvio dgcAˉ cells.ConclusionsThe study reveals a novel role for c-di-GMP in aggregation, while the reduced spore number in Pvio and Ppal dgcAˉ is likely an indirect effect, due to depletion of the cell pool by the extended stalk formation. The results indicate that in addition to c-di-GMP, Dictyostelia ancestrally used an as yet unknown factor for induction of stalk formation. The activation of AcaA by c-di-GMP is likely conserved throughout Dictyostelia.