Pattern Of Decline Research Articles

Trade Wars and Disrupted Global Commodity Chains

The literatures on global commodity chains and global value chains rest on an unquestioned assumption: the continual expansion of globalization. The Trump Administration's trade wars challenged this foundational assumption and even today the new Biden regime also hints at the shift away from global supply chains. We find that the prior administration’s efforts caused continued disruption of long-established commodity chains in steel, aluminum, automobiles, and other manufactured products. Flows of raw materials, intermediate products and components, and finished goods now confront higher costs. Firms continue efforts to restructure commodity chains in ways that will require the disarticulation of some nodes and the creation of new nodes. We claim that these trade wars and breakdown of global commodity chains (GCCs) may in fact mark the start of the breakdown of the U.S.-led world order. This shift harkens the onset of a new era of economic and geopolitical conflict. A key question: has this disruption of old patterns and rise of new ones continued in the post-Trump era? Does the familiar pattern of globalization continue – or is competition, contestation and disarticulation leading to sectoral economic changes that drive larger patterns of economic ascent, dominance, and decline in the world economy?

Genomic tools for comparative conservation genetics among three recently diverged stag beetles (Lucanus, Lucanidae)

Abstract We are witnessing a rapid decline in global biodiversity. International protocols and local conservation laws have been installed to counter such an unprecedent rate of decline. However, quantitatively evaluating how much biodiversity has been lost due to climatic and anthropogenic effects and how much biodiversity has been restored due to conservation efforts remains challenging. We applied a comparative conservation genomic approach to statistically and quantitatively address these questions using three geographical taxa from a stag beetle species complex. We found that the three sky‐island taxa formed three independently evolving units without detectable post‐divergence gene flow; furthermore, the three taxa, which have been divergent from each other since the mid‐Pleistocene, have experienced episodes of demographic decline in the past. More importantly, even though idiosyncratic anthropogenic exploitations have been hypothesised to impact the recent demographic history (<100 years) differently, we found a shared pattern of continuous decline in effective population size among the three geographical taxa. We argue that future empirical studies should include more taxa, in addition to the focal species, that may or may not be affected by the focal historical events to avoid making biased conservation plans.

Sex-specific differences in the effect of lymphocyte-to-C-reactive protein ratio on subclinical myocardial injury in the general population free from cardiovascular disease

Background and aimThe Lymphocyte-to-C-reactive protein ratio (LCR) combines information on immune and inflammatory status. Lymphocytes reflect immune health, while C-reactive protein (CRP) signals systemic inflammation. Some studies have linked LCR with cardiovascular outcomes, suggesting it could help identify at-risk individuals. However, its clinical utility needs further research validation. To investigate the association between lymphocyte-to-C-reactive protein ratio (LCR) and subclinical myocardial injury (SC-MI) in individuals who are free from cardiovascular disease (CVD) within the general population. Methods and resultsThe study included individuals in the National Health and Nutrition Examination Survey (NHANES) III. SC-MI was defined as having a Cardiac Infarction Injury Score (CIIS) greater than 10 units on a 12-lead electrocardiogram. Logistic regression models were employed to investigate the association between LCR and SC-MI. In total, 5870 individuals were included in the study, among whom 3266 had a history of SC-MI. Compared with the lowest quartile (Q1) in male, the odds ratios (OR) of SC-MI in Q2, Q3, and Q4 were 0.67 (95%CI: 0.53–0.86), 0.66 (95%CI: 0.51–0.84), and 0.70 (95%CI: 0.55–0.89), respectively. The data shows a trend where the OR of SC-MI are lower in higher quartiles of LCR, compared to the lowest quartile, in the male population (P for trend = 0.006). In other words, the likelihood of SC-MI tends to be lower among males with higher LCR values. However, after adjusting for potential confounding variables, the relationship between LCR and SC-MI displays a pattern of an initial decline, followed by a minor upward shift. ConclusionLCR is independently and inversely associated with SC-MI risk in the general population free from CVD. Furthermore, the observed association is exclusive to males, indicating a need for further randomized controlled trials to substantiate the efficacy of implementing LCR reduction as a means of CVD prevention in the male population.

Long term monitoring reveals the importance of large, long unburnt areas and smaller fires in moderating mammal declines in fire‐prone Savanna of northern Australia

Abstract Biodiversity loss is often attributable to multiple interacting pressures that are moderated across environmental gradients. These processes contribute to complex responses that are challenging to interpret and understand. Well‐designed and well‐implemented monitoring can play a vital role in this but is rarely undertaken. Mounting evidence suggests that current fire regimes across Savanna ecosystems have contributed to the decline of a range of biota. Hence, contemporary fire regimes are at odds with conservation goals. Using an extensive spatiotemporal monitoring dataset from three large National Parks in northern Australia, we applied generalised linear mixed models to examine: (1) trends in mammal richness and abundance through time and variation across environmental gradients such as productivity or landscape position (e.g. terrain ruggedness); and (2) how fire, a potential driver, is moderated by environmental gradients. Across 24 years, major declines in mammal richness and abundance were observed with greater reductions in less rugged and less mesic habitats. Patterns of decline were related to multiple aspects of fire regimes, but not changes in vegetation structure and composition, or cane toads, Rhinella marina, arrival and concomitant poisoning of predatory animals during consumption. More pronounced declines occurred in sites that were exposed to larger fires, had less long unburnt (>5 years without fire) vegetation and were more distant from large, long unburnt patches. Relationships between mammal persistence and fire varied among vegetation communities, with the strongest fire effects observed in lowland woodland—drier with few barriers to fire spread—where the availability of long unburnt areas moderated declines more than in other vegetation communities. Synthesis and applications. Current fire regimes are contributing to mammal declines in northern Australian Savanna. Collectively, our results highlight: (1) the value of long term monitoring, and importance of considering landscape position when assessing faunal responses to landscape‐level perturbations like fire; (2) that significant improvements in fire regimes are required to ameliorate mammal declines; and (3) the need to shift management focus from retaining small, short‐lived unburnt patches toward preserving relatively large contiguous areas of long unburnt habitat, particularly in less rugged lowland and sandstone woodlands.

Rethinking Urban Decline in Post-COVID19: Bibliometric Analysis and Countermeasures

Urban decline refers to the sustained deterioration of cities in terms of their economy, population, and social aspects. The outbreak of the Coronavirus Disease 2019 (COVID-19) pandemic in 2019 objectively affected the trajectory of this phenomenon. A comprehensive analysis of scientific research on urban decline and its practical implications was conducted using bibliometric methods, data acquired from 2019 to 2023 and the Web of Science. Since COVID-19, research on urban decline has been predominantly led by traditional developed countries such as the United States and England, with a high degree of regional collaboration. Keyword clusters have focused on urban regeneration, growth, decay, family planning, resource dependency theory, public art, etc. Keyword co-occurrence has focused on shrinking cities, gentrification policy, land use, etc. Based on previous analyses and the contemporary context, the intrinsic logic behind the urban decline in recent years can be summarized as inadequate economic development, lagging infrastructure construction, the siphoning effect of core regional cities, and unique institutional factors leading to specific urban decline patterns. Comprehensive urban recovery plans have been proposed, including reshaping urban spatial layouts and planning and strengthening strategies for social and economic revival, with correspondence-specific samples. Studying the impact of COVID-19 on urban decline from the perspectives of city development and strategies can help us better understand the repercussions of global health crises on cities, providing a more scientific basis for urban planning and management to build resilient, sustainable, and equitable cities.

Gender differences in the impact of the COVID-19 pandemic on psychological well-being: evidence from Japan

ABSTRACT We advance research on the ‘gendered pandemic’ and its implications for psychological well-being in three important ways. First, we focus on Japan, arguably the most gender-inegalitarian wealthy country. Second, we focus on gender differences in both hedonic and eudaimonic well-being. Third, we use demographic decomposition tools to evaluate the extent to which observed gender differences in decline in psychological well-being reflect differences in pre-pandemic characteristics, differences in life changes during the pandemic, differences in pandemic-related worry, and differences in men’s and women’s responses to these characteristics and experiences. Results show that decline in both dimensions of psychological well-being was significantly greater for women and that the contributions of differences in relationships were larger than those of differences in composition. We also show that reduction in well-being derived from social interaction was particularly pronounced for women and that gender differences in age patterns of decline in both dimensions of psychological well-being are large.

DISTRIBUTION AND ANTIBACTERIAL RESISTANCE OF WOUND PATHOGENIC BACTERIA IN PATIENTS OF SANA’A HOSPITALS, YEMEN

Background and objectives: Cutaneous wounds are a common symptom in human medical practice. Understanding the physiology of the wound healing process and using the right therapeutic intervention are necessary for managing the existing healing in wound patients. Infection can cause wounds to take longer to heal, cosmetic surgery outcomes to be less satisfactory, and medical expenses to rise. Due to the dearth of studies in Yemen and other Arabic-nations that describe the different forms, locations, and current understanding of the bacterial causes of wound infection. So, general care hospitals in Sana'a, Yemen, undertook a study to identify the different types, locations, and prevalence of wound contamination caused by various bacteria, as well as to examine the antibiotic susceptibility pattern of wound-isolated bacteria. Subjects and methods: This cross-sectional study was carried out among 699 wound patients with clinically diagnosed wound infections at NCPHL during the years 2021-2022. Pus and wound swab samples were processed using standard microbiological procedures at NCPHL. A modified Kirby Bauer disc diffusion technique was used to investigate the susceptibility of bacteria to various antibiotics. From pre-questionnaire and laboratory records of the NCPHL, clinical information about patients was gathered, including the types and locations of wounds. Results: Out of 699 samples, 580 (82.98%) were positive for bacterial cultures. The most common wound was postoperative (30.8%), followed by diabetic foot ulcer (24.5%), traumatic wound (18.7%) and bullet wound (16.9%), while it was less frequent for caesarean section (5.7%) and sharp cut (2%). The present study revealed that Gram-negative bacteria were less frequent than Gram-positive bacteria (43.3% vs. 56.7%). Also gram-positive bacteria show a very high percentage (92.1%) of multidrug resistant (MDR) in compared to gram-negative bacteria (37.8%). Conclusion: In the current study's wound bacteriological profile, Staphylococcus aureus was shown to be highly prevalent, followed by Escherichia coli, S. epidermidis (CoNS), Acinobacter spp., and Pseudomonas aeruginosa. Their sensitivity to widely used antibiotics showed a pattern of decline. It is crucial to be informed of the current bacterial profile trend and to adjust the antibiotic schedule in accordance with sensitivity. Peer Review History: Received: 4 March 2023; Revised: 26 April; Accepted: 20 June 2023, Available online: 15 July 2023 Academic Editor: Dr. A.A. Mgbahurike, University of Port Harcourt, Nigeria, amaka_mgbahurike@yahoo.com Received file: Reviewer's Comments: Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 7.0/10 Reviewers: Dr. Sheikh Abdul Khaliq, Department of Pharmacy Practice, Faculty of Pharmacy, Hamdard University, Karachi, Pakistan, drsheikh1974@gmail.com Dr. Wadhah Hassan Ali Edrees, Hajja University, Yemen, edress2020@gmail.com Dr. Bilge Ahsen KARA, Ankara Gazi Mustafa Kemal Hospital, Turkey, ahsndkyc@gmail.com

Age-related gene expression signatures from limb skeletal muscles and the diaphragm in mice and rats reveal common and species-specific changes

BackgroundAs a result of aging, skeletal muscle undergoes atrophy and a decrease in function. This age-related skeletal muscle weakness is known as “sarcopenia”. Sarcopenia is part of the frailty observed in humans. In order to discover treatments for sarcopenia, it is necessary to determine appropriate preclinical models and the genes and signaling pathways that change with age in these models.Methods and resultsTo understand the changes in gene expression that occur as a result of aging in skeletal muscles, we generated a multi-time-point gene expression signature throughout the lifespan of mice and rats, as these are the most commonly used species in preclinical research and intervention testing. Gastrocnemius, tibialis anterior, soleus, and diaphragm muscles from male and female C57Bl/6J mice and male Sprague Dawley rats were analyzed at ages 6, 12, 18, 21, 24, and 27 months, plus an additional 9-month group was used for rats. More age-related genes were identified in rat skeletal muscles compared with mice; this was consistent with the finding that rat muscles undergo more robust age-related decline in mass. In both species, pathways associated with innate immunity and inflammation linearly increased with age. Pathways linked with extracellular matrix remodeling were also universally downregulated. Interestingly, late downregulated pathways were exclusively found in the rat limb muscles and these were linked to metabolism and mitochondrial respiration; this was not seen in the mouse.ConclusionsThis extensive, side-by-side transcriptomic profiling shows that the skeletal muscle in rats is impacted more by aging compared with mice, and the pattern of decline in the rat may be more representative of the human. The observed changes point to potential therapeutic interventions to avoid age-related decline in skeletal muscle function.

Developing a High-Resolution Seamless Surface Water Extent Time-Series over Lake Victoria by Integrating MODIS and Landsat Data

To effectively monitor the spatio–temporal dynamics of the surface water extent (SWE) in Lake Victoria, this study introduced a novel methodology for generating a seamless SWE time series with fine resolution by integrating daily a Moderate-resolution Imaging Spectroradiometer (MODIS) and Landsat imagery. In the proposed methodology, daily normalized difference vegetation index (NDVI) time series data with 30 m resolution were first generated based on the constructed pixel-by-pixel downscaling models between the simultaneously acquired MODIS-NDVI and Landsat-NDVI data. In the compositing process, a Minimum Value Composite (MinVC) algorithm was used to generate monthly minimum NDVI time series, which were then segmented into a seamless SWE time series of the years 2000–2020 with 30 m resolution from the cloud background. A comparison with the existing Landsat-derived JRC (European Joint Research Centre) monthly surface water products and altimetry-derived water level series revealed that the proposed methodology effectively provides reliable descriptions of spatio–temporal SWE dynamics. Over Lake Victoria, the average percentage of valid observations made using the JRC’s products was only about 70% due to persistent cloud cover or linear strips, and the correlation with the water level series was poor (R2 = 0.13). In contrast, our derived results strongly correlated with the water level series (R2 = 0.54) and efficiently outperformed the JRC’s surface water products in terms of both space and time. Using the derived SWE data, the long-term and seasonal characteristics of lake area dynamics were studied. During the past 20 years, a significant changing pattern of an initial decline followed by an increase was found for the annual mean SWE, with the lowest area of 66,386.57 km2 in 2006. A general seasonal variation in the monthly mean lake area was also observed, with the largest SWE obtained during June–August and the smallest SWE observed during September–November. Particularly in the spring of 2006 and the autumn of 2020, Lake Victoria experienced intense episodes of drought and flooding, respectively. These results demonstrate that our proposed methodology is more robust with respect to capturing spatially and temporally continuous SWE data in cloudy conditions, which could also be further extended to other regions for the optimal management of water resources.

African election management bodies in the era of democratic backsliding

ABSTRACT Although democratisation has evolved unevenly across Africa since the 1990s, there has been progress in the establishment and strengthening of independent election management bodies (EMBs). Since the mid-2000s, scholars and analysts have identified a global trend toward democratic backsliding, characterised in part by the erosion of democratic institutions. Such a trend might be expected to pose significant threats to EMBs. This article contributes new insights through a review of data from the Perceptions of Electoral Integrity and Varieties of Democracy projects. While it finds wide variation in EMB performance and autonomy, there is no overall pattern of decline that might be associated with democratic backsliding in Africa. Case analysis of Ghana and Zambia further demonstrates that the challenges EMBs face are multifaceted and not only driven by anti-democratic leaders. Co-ordinated efforts are therefore needed to strengthen EMB autonomy and capacity to (re)build trust and deliver elections with integrity.

Post-Pandemic Onset Public School Enrollment and Mobility: Evidence From Virginia

Public school enrollment dramatically decreased during the pandemic, but the patterns of decline and student movement across schools are not yet well understood. Using statewide student-level data from Virginia, we find pre-K–12 enrollment dropped by 4% between fall 2019 and the first post-pandemic fall of 2020. The changes were the largest in pre-kindergarten and kindergarten and explained mostly by decreases in new enrollees, though exits also increased. K–12 enrollment declines were the largest among White and economically-advantaged students (but largest for Black and economically-disadvantaged pre-kindergartners). We also observe a decline in school transfers (both within and between districts), concentrated among Black and economically-disadvantaged students and students with disabilities. Findings have implications for equity, school funding, and student well-being.

Visuospatial and Verbal Memory Differences in Amish Individuals With Alzheimer Disease and Related Dementias.

Verbal and visuospatial memory impairments are common to Alzheimer disease and Related Dementias (ADRD), but the patterns of decline in these domains may reflect genetic and lifestyle influences. The latter may be pertinent to populations such as the Amish who have unique lifestyle experiences. Our data set included 420 Amish and 401 CERAD individuals. Sex-adjusted, age-adjusted, and education-adjusted Z-scores were calculated for the recall portions of the Constructional Praxis Delay (CPD) and Word List Delay (WLD). ANOVAs were then used to examine the main and interaction effects of cohort (Amish, CERAD), cognitive status (case, control), and sex on CPD and WLD Z-scores. The Amish performed better on the CPD than the CERAD cohort. In addition, the difference between cases and controls on the CPD and WLD were smaller in the Amish and Amish female cases performed better on the WLD than the CERAD female cases. The Amish performed better on the CPD task, and ADRD-related declines in CPD and WLD were less severe in the Amish. In addition, Amish females with ADRD may have preferential preservation of WLD. This study provides evidence that the Amish exhibit distinct patterns of verbal and visuospatial memory loss associated with aging and ADRD.

Evaluation of the usefulness of a paper–pencil group cognitive assessment for older adults in the community

BackgroundAs the older population increases, the need for early detection of cognitive decline is also increasing. In this study, we examined whether our paper–pencil type group examination for cognitive assessment (PAPLICA) could detect the effects of years of education and aging.MethodsPAPLICA was conducted on 829 older people. The inclusion criteria were age 60 years or older and the ability to come to the event site alone. The exclusion criteria were participants with a medical or psychiatric disorder or dementia.One examiner conducted the test on a group of approximately 10–20 people in approximately 25 min. Participants were instructed on tackling the issues projected on the projector, and their answers were recorded in a response booklet.ResultsAn independent sample t-test was performed for years of education, and ANCOVA was performed for aging. Among the test items included in PAPLICA, the Speed I and Letter fluency tests were unable to detect the effects of aging. Furthermore, the age at which the effect of aging manifests varies depending on the test item. For instance, a decline in scores in the Speed I and Picture ECR Free recall tests was observed in the 70–74 age group; for that of Word DRT, Picture ECR cued recall, and Similarity, in the 75–79 age group; for CFT, in the 80–84 age group, and for CLOX, the decline was observed in the 85 ≤ age group.ConclusionsPAPLICA, similar to other neuropsychological tests, was able to detect the effects of years of education and aging. Future testing should be conducted on different demographics to identify the differences in patterns of cognitive decline.

Demographic turnover can be a leading driver of hierarchy dynamics, and social inheritance modifies its effects.

Individuals and societies are linked through a feedback loop of mutual influence. Demographic turnover shapes group composition and structure by adding and removing individuals, and social inheritance shapes social structure through the transmission of social traits from parents to offspring. Here I examine how these drivers of social structure feedback to influence individual outcomes. I explore these society-to-individual effects in systems with social inheritance of hierarchy position, as occur in many primates and spotted hyenas. Applying Markov chain models to empirical and simulated data reveals how demography and social inheritance interact to strongly shape individual hierarchy positions. In hyena societies, demographic processes-not status seeking-account for the majority of hierarchy dynamics and cause an on-average lifetime decline in social hierarchy position. Simulated societies clarify how social inheritance alters demographic effects-demographic processes cause hierarchy position to regress to the mean, but the addition of social inheritance modifies this pattern. Notably, the combination of social inheritance and rank-related reproductive success causes individuals to decline in rank over their lifespans, as seen in the hyena data. Further analyses explore how 'queens' escape this pattern of decline, and how variation in social inheritance generates variability in reproductive inequality. This article is part of the theme issue 'Evolutionary ecology of inequality'.

413-P: Intensive Insulin Therapy Delays the “Breakpoint” to Progressive Kidney Function Decline—New Findings and Implications of eGFR Trajectory Analysis in DCCT/EDIC Data

Patterns of kidney function decline vary among those with T1D. End-stage kidney disease (ESKD) develops after progressive kidney function decline that begins when kidney function is normal, regardless of albuminuria. We aimed to determine if these findings were observed in the DCCT/EDIC cohort, which enrolled 1,441 individuals and randomly assigned them to intensive insulin therapy (n=711) or conventional insulin therapy (n=730). Baseline mean eGFR and AER were 125 ml/min/1.73m2 and 12 mg/24 hours, respectively. During 27 years of follow-up 129 individuals reached reduced eGFR <60ml/min/1.73m2 or ESKD. For these individuals we applied latent class trajectory analysis minimizing sum of squares of linear spline models with varying knot placement to identify patterns of eGFR decline. We identified two patterns: i) slow decline without eGFR breakpoint (n=56) and ii) fast decline with clear breakpoint (n=73). Slow decliners reached reduced eGFR but rarely ESKD (2%), while many fast decliners progressed to ESKD (35%) within 5-15 years after the breakpoint. Fast decline was less frequent in intensive compared to conventional insulin therapy [26 (3.7%) vs 47 (6.4%), respectively, p=0.022] and had longer median time from enrollment to breakpoint (18 vs 13 years, respectively, p=0.0004). However, the slope of annual loss of eGFR after breakpoint did not differ. In conclusion, we identified a unique phenotype - the “breakpoint” to fast decline in eGFR - as the main predictor of ESKD in T1D. This breakpoint started while eGFR was normal, subsequent decline was linear, and the onset of the breakpoint was substantially delayed by intensive insulin therapy rather than the slope of decline itself. Research on biomarkers that predict the onset of the eGFR ‘breakpoint’ is needed. Disclosure K.Ihara: None. J.K.Skupien: None. E.Satake: None. B.A.Perkins: Advisory Panel; Dexcom, Inc., Insulet Corporation, Novo Nordisk, Sanofi, Vertex Pharmaceuticals Incorporated, Other Relationship; Abbott, Medtronic, Sanofi, Research Support; Novo Nordisk, Bank of Montreal (BMO). A.Krolewski: None.

#3892 AGE-RELATED TRAJECTORY PATTERN OF HANDGRIP STRENGTH AND MORTALITY IN PATIENTS ON HEMODIALYSIS

Abstract Background and Aims Muscle weakness is a factor known to worsen prognosis in patients on hemodialysis [1], and the prevention of muscle weakness is extremely important in disease management. In particular, understanding age-related changes in muscle strength can be advantageous for long-term interventions. A previous study on community-dwelling older adults examined sex-specific age trends in muscle strength in order to identify potential trajectory patterns, and it showed that muscle strength tended to display similar age-related changes later in life regardless of the baseline level. Additionally, individuals in the low trajectory group had a higher mortality risk than did the high trajectory group [2]. However, reports examining longitudinal trajectories of muscle strength in patients on hemodialysis are limited, and their association with life prognosis remains unclear. Therefore, this study aimed to identify sex-specific aging patterns of handgrip strength as an indicator of muscle strength in patients on hemodialysis and to further investigate their association with life prognosis. Method Patients on hemodialysis with a minimum of two available measurements of handgrip strength between the years 2002 and 2022 were analyzed. In total, 544 patients (age: 65.1±11.9 years, 59.5% male, total observation data: 2,499) were enrolled in this study. Aging patterns of handgrip strength were classified by sex using group-based semiparametric mixture modeling. The association between typed aging patterns of handgrip strength and all-cause mortality was examined using Cox regression analysis after adjusting for the baseline age, body mass index, dialysis history, comorbidity index score, and hemoglobin and albumin levels. The statistical significance level was set at 5%. Results Age-related trajectory patterns of handgrip strength in men and women were categorized into three groups, low, middle, and high, as shown in Fig. 1. All three groups showed an age-related decline. The “low group” showed a reduction in handgrip strength (<28 kg for men and <18 kg for women) from baseline and continued to decline thereafter. The “middle group” did not show any decline at baseline, but decline was noted after 65 years of age. The “high group” displayed a decline in handgrip strength after 80 years of age, despite high handgrip strength at baseline. 23.9%, 60.1%, and 16.0% for men and 30.1%, 46.3%, and 23.7% for women were assigned to the low, middle, and high groups, respectively. When the high group was used as the reference group, the low groups showed a significantly higher mortality risk after adjusting for confounders in both men and women (men; p = 0.03, women; p<0.001). Conclusion In patients on hemodialysis, age-related decline of handgrip strength was observed in both men and women, regardless of baseline values. Among the three patterns of decline, the low group had a higher mortality rate compared to the high group in both men and women. The results suggest that even if decline in muscle weakness over time can be expected, handgrip strength needs to be improved in order to improve life prognosis.

Decline in emergency department visits during the COVID-19 quarantine

BackgroundEmergency department (ED) visits can be divided into urgent and non-urgent. A delay in seeking medical help, especially in urgent cases, can lead to fatal consequences, along with a higher rate of complications and morbidity. Coronavirus disease 2019 (COVID-19) pandemic spread led to restrictions and eventually quarantines. We investigated the impact of the COVID-19 spread and quarantine on ED visits rates comparing to parallel periods in preceding years (2013–2019). In addition, we compared this decrease to holidays and weekends, times in which a decrease in ED visits is seen. MethodsThis was a descriptive retrospective study. Causes of ED referrals were divided into urgent and non-urgent, then into different subcategories including infectious, cardiac, etc. ResultsFor the spring COVID-192020 quarantine period, a 56.3% decrease of mean ED visits per day was seen, as compared to preceding years (55.7% and 98.9% respectively). This decrease was also statistically evident when comparing the urgent and non-urgent causes separately and for all sub-categories. This pattern of decrease also showed statistical evidence of fewer ED visits during holidays for most comparisons, in which lower ED visit rates are expected. Significantly lower rates of ED visits were demonstrated during the COVID-19 quarantine period, as compared to preceding years and main holidays and weekends, a decrease that was also demonstrated for urgent life-threatening causes. ConclusionOur findings can be used to inform a wide range of stakeholders, including regional planners, historians, sociologists, and international healthcare organizations. Healthcare providers should understand the reasons for this ED visit decline pattern, attempt to address patients' concerns, and increase awareness regarding alarming symptoms in urgent medical situations.

Development and validation of an ultrahigh-performance liquid chromatography-tandem mass spectrometry method to investigate the plasma pharmacokinetics of a KCa 2.2/KCa 2.3 positive allosteric modulator in mice.

There is currently no treatment for spinocerebellar ataxias (SCAs), which are a group of genetic disorders that often cause a lack of coordination, difficulty walking, slurred speech, tremors, and eventually death. Activation of KCa 2.2/KCa 2.3 channels reportedly exerts beneficial effects in SCAs. Here, we report the development and validation of an analytical method for quantitating a recently developed positive allosteric modulator of KCa 2.2/KCa 2.3 channels (compound 2q) in mouse plasma. Mouse plasma samples (10 μL) containing various concentrations of 2q were subjected to protein precipitation in the presence of a structurally similar internal standard (IS). Subsequently, the analytes were separated on a C18 ultrahigh-performance liquid chromatography column and detected by a tandem mass spectrometer. The method was validated using US Food and Drug Administration (FDA) guidelines. Finally, the validated assay was applied to the measurement of the plasma concentrations of 2q in plasma samples taken from mice after single intravenous doses of 2mg/kg of 2q, and the pharmacokinetic parameters of 2q were determined. The calibration standards were linear (r2 ≥ 0.99) in the range of 1.56-200 nM of 2q with intra- and inter-run accuracy and precision values within the FDA guidelines. The lower limit of quantitation of the assay was 1.56 nM (0.258 pg on the column). The recoveries of 2q and IS from plasma were >94%, with no appreciable matrix effect. The assay showed no significant carryover, and the plasma samples stored at -80°C or the processed samples stored in the autosampler at 10°C were stable for at least 3 weeks and 36 h, respectively. After intravenous injection, 2q showed a bi-exponential decline pattern in the mouse plasma, with a clearance of 30 mL/min/kg, a terminal volume of distribution of 1.93 mL/kg, and a terminal half-life of 45 min. The developed assay is suitable for preclinical pharmacokinetic-pharmacodynamic studies of 2q as a potential drug candidate for ataxias.

Trends in U.S and global patient enrollment from 2014 to 2022 in lung cancer clinical trials supporting marketing applications: An FDA analysis.

1576 Background: Oncology drug development is an increasingly global endeavor, however it is unclear how enrollment in registrational clinical trials for lung cancer have been impacted. Clinical trial data must be reflective of the intended population in order to be considered applicable to U.S patients and medical practice, and for FDA review. Methods: Registrational clinical trials supporting lung cancer indications submitted to FDA from 2014 to 2022 were included. Patient enrollment per country was extracted for each trial, and countries were grouped into 9 global regions. The proportion of patients enrolled in the U.S and global regions were calculated for each trial. For the purpose of this analysis, MRCTs were defined as trials that enrolled at least 5% of patients from each of ≥ 3 global regions with no region accounting for ≥ 70% of patient enrollment. Trial-level patient enrollment was aggregated into 3 triennia: 2014-2016, 2017-2019, and 2020-2022. Results: A total of 66 pivotal trials supporting 59 applications submitted to FDA were evaluated during the study period. Of these, 91% ( n=60) were for non-small cell lung cancer while 9% ( n=6) were for small cell lung cancer; 59% ( n=39) were randomized controlled trials (RCTs) while 41% ( n=27) were single-arm trials; 53% ( n=35) were for biologics while 47% ( n=31) were for non-biologics; and 86% ( n=30) of the biologics-based regimens were anti-programmed death (ligand)-1 antibody-containing regimens. The proportion of trials with no U.S patient enrollment increased from 4.8% in 2014-2016 to 19.0% in 2020-2022 while those with ≥ 10% U.S patient enrollment declined from 71.4% in 2014-2016 to 52.3% in 2020-2022. There was a decline in the proportion of trials conducted as MRCTs since 2014 from 85.7% in 2014-2016 to 66.7% in 2020-2022. Conclusions: This exploratory analysis suggests that there may be declining U.S patient enrollment in lung cancer pivotal trials, and the proportion of these trials conducted as MRCTs may also be declining. These patterns of decline appear to be driven by the countries selected for patient enrollment in RCTs rather than in single-arm trials. Pivotal trials that do not enroll U.S patients and are not conducted as true MRCTs may have limited applicability to U.S patients.[Table: see text]

Shale oil enrichment evaluation and production law in Gulong Sag, Songliao Basin, NE China

Based on the results of drilling, tests and simulation experiments, the shales of the Cretaceous Qingshankou Formation in the Gulong Sag of the Songliao Basin are discussed with respect to hydrocarbon generation evolution, shale oil occurrence, and pore/fracture evolution mechanism. In conjunction with a substantial amount of oil testing and production data, the Gulong shale oil enrichment layers are evaluated and the production behaviors and decline law are analyzed. The results are drawn in four aspects. First, the Gulong shales are in the stage of extensive hydrocarbon expulsion when Ro is 1.0%–1.2%, with the peak hydrocarbon expulsion efficiency of 49.5% approximately. In the low–medium maturity stage, shale oil migrates from kerogen to rocks and organic pores/fractures. In the medium–high maturity stage, shale oil transforms from adsorbed state to free state. Second, the clay mineral intergranular pores/fractures, dissolution pores, and organic pores make up the majority of the pore structure. During the transformation, clay minerals undergo significant intergranular pore/fracture development between the minerals such as illite and illite/smectite mixed layer. A network of pores/fractures is formed by organic matter cracking. Third, free hydrocarbon content, effective porosity, total porosity, and brittle mineral content are the core indicators for the evaluation of shale oil enrichment layers. Class-I layers are defined as free hydrocarbon content equal or greater than 6.0 mg/g, effective porosity equal or greater than 3.5%, total porosity equal or greater than 8.0%, and brittle mineral content equal or greater than 50%. It is believed that the favourable oil layers are Q2–Q3 and Q8–Q9. Fourth, the horizontal wells in the core area of the light oil zone exhibit a high cumulative production in the first year, and present a hyperbolic production decline pattern, with the decline index of 0.85–0.95, the first-year decline rate of 14.5%–26.5%, and the single-well estimated ultimate recovery (EUR) greater than 2.0×104 t. In practical exploration and production, more efforts will be devoted to the clarification of hydrocarbon generation and expulsion mechanisms, accurate testing of porosity and hydrocarbon content/phase of shale under formation conditions, precise delineation of the boundary of enrichment area, relationship between mechanical properties and stimulated reservoir volume, and enhanced oil recovery, in order to improve the EUR and achieve a large-scale, efficient development of shale oil.