Lag Period Research Articles

Enhanced Methanogenesis of Waste-Activated Sludge (WAS) in a Continuous Stirring Tank Reactor with Stealth Electrodes

The integration of a microbial electrolysis cell (MEC) is an effective strategy for enhancing the efficiency and stability of an anaerobic digestion (AD) system for energy recovery from waste-activated sludge (WAS). Typically, electrodes are arranged as separate components, potentially disrupting mixing and complicating the reactor configuration, posing challenges for the scaling up of AD-MEC coupling systems. In this study, electrodes were introduced into a continuous stirring tank reactor (CSTR) in a “stealth” manner by integrating them with the inner wall and stirring paddle. This electrode arrangement approach was validated through a sequential batch digestion experiment, resulting in a remarkable 1.5-fold increase in cumulative methane production and a shortened lag period compared to the traditional CSTR with a nonconductive inner wall and stirring paddle. Both the conductive materials (CMs) employed in the electrodes and the electrochemical processes equally contributed to the observed enhancement effect of the electrodes by regulating the evolution of the microbial community within the electrode biofilms, with a specific emphasis on the enrichment of methanogens (primarily Methanobacterium). This research offers a potential avenue to solve the contradiction between the electrode introduction and the mixing operation in AD-MEC coupling systems and to contribute to its future commercial application.

FORMULATION AND EVALUATION OF MODIFIED PULSATILE CAPSULE FOR CHRONOPHARMACOTHERAPY OF RHEUMATOID ARTHRITIC PAIN

Objective: The objective of the present study was to design and evaluate pulsincap system for chrono pharmacotherapy of rheumatoid arthritis that combines advantages of both immediate and sustained release technology with the suitable delay of drug release. Methods: Pulsatile drug delivery system based on pulsincap® technology was designed using mucoadhesive microspheres and Tramadol bilayer tablet plugs. The drug-excipient interaction was carried out by FTIR. Hardness, thickness, lag time, and swelling index all play a role in optimizing tablet plugs. The microspheres were examined for parameters such as particle size, surface morphology, encapsulation efficiency, swelling index, % mucoadhesion, and in vitro dissolution. Results: In modified pulsincaps, bilayer tablet plug shows drug release within 40 min and hydrogel plugs shows good swelling index and suitable lag time. In microspheres formulations, MF9 is the most suitable among them as it shows better drug content, particle size, surface morphology, in vitro drug release, and release kinetics. The drug is released right away, followed by the dissolution of the enteric coating at pH 6.8, followed by a suitable delay of 6 hours, and then the maximum amount of drug release is 99.62% at the end of 10th h. Conclusion: The pulsatile delivery system developed with HPMCK4M and tamarindus gum as plugging material showed a satisfactory lag period when compared to Tamarindus gum alone. Drug release can be achieved from treated gelatin capsule and hydrogel plug for a prolonged period by MF9 formulation.

Inhibition of norfloxacin on fermentative hydrogen production: Performance evaluation and metagenomic analysis

Toxic chemicals can inhibit the dark fermentation process for renewable biohydrogen production. Norfloxacin (NOR), a typical antibiotic, is present in various feedstocks of dark fermentation, which has excellent antibacterial properties. It is hypothesized that NOR could cause adverse effects on fermentative hydrogen production, while current understanding of this subject is scare. This study investigated the potential inhibitory effect of NOR on dark hydrogen fermentation, and explored the underlying mechanisms from the perspectives of bacterial community structure and functional gene abundance. The results showed that NOR significantly reduced the hydrogen-producing capacity upon exposure to concentrations exceeding 10 mg/L. The hydrogen yield decreased from 1.56 to 0.27 H2/mol-glucose at NOR concentrations of 50 mg/L. NOR also prolonged the hydrogen-producing lag period. Bacterial community analysis revealed that NOR reduced the abundance of high-yielding H2-generating bacteria, such as Clostridium sp., while increasing the abundance of H2-consuming bacteria (e.g. Enterococcus sp.). Metagenomic analysis further indicated that crucial genes involved in glycolysis (e.g. HK, tal-pgi, pfk and PK) and hydrogen formation (e.g. por and E1.12.7.2) were remarkably downregulated under NOR exposure, essentially causing the inhibition of hydrogen production. This study contributes to a better understanding of how antibiotics inhibit dark hydrogen fermentation and provides a theoretical basis for reducing potential inhibitory effects.

Efficient conversion of cane molasses into Tremella fuciformis polysaccharides with enhanced bioactivity through repeated batch culture

Tremella fuciformis polysaccharide (TFPS) is a natural mushroom mucopolysaccharide widely used in health foods, medical care, cosmetic and surgical materials. In this study, we developed an efficient strategy for the repeated batch production of highly bioactive TFPS from the agro-industrial residue cane molasses. Cane molasses contained 39.92 % sucrose (w/w), 6.36 % fructose and 3.53 % glucose, all of which could be utilized by T. fuciformis spores, whereas, the TFPS production efficiency only reached 0.74 g/L/d. Corn cobs proved to be the best immobilized carrier that could tightly absorb spores and significantly shorten the fermentation lag period. The average yield of TFPS in eight repeated batch culture was 5.52 g/L with a production efficiency of 2.04 g/L/d. The average fermentation cycle after optimization was reduced by 61.61 % compared with the initial conditions. Compared to glucose as a carbon source, cane molasses significantly increased the proportion of low-molecular-weight TFPS (TFPS-2) in total polysaccharides from 3.54 % to 17.25 % (w/w). Moreover, TFPS-2 exhibited potent antioxidant capacity against four free radicals (O2−, ABTS+, OH, and DPPH). In conclusion, this study lays the foundation for the efficient conversion of cane molasses and production of TFPS with high bioactivity.

Risk of Coccidioidomycosis Infection Among Individuals Using Biologic Response Modifiers, Corticosteroids, and Oral Small Molecules.

The study objective was to examine associations between the use of biologic response modifiers (BRMs), corticosteroids, and oral small molecules (OSMs) and subsequent coccidioidomycosis infection risk among US Medicare beneficiaries with rheumatic or autoimmune diseases. This retrospective cohort study used US 2011 to 2016 Medicare claims data. We identified geographic areas with endemic coccidioidomycosis (≥25 cases per 10,000 beneficiaries). Among beneficiaries having any rheumatic/autoimmune diseases, we identified those initiating BRMs, corticosteroids, and OSMs. Based on refill days supplied, we created time-varying exposure variables for BRMs, corticosteroids, and OSMs with a 90-day lag period after drug cessation. We examined BRMs, corticosteroids, and OSMs and subsequent coccidioidomycosis infection risk using multivariable Cox proportional hazard regression. Among 135,237 beneficiaries (mean age: 67.8 years; White race: 83.1%; Black race: 3.6%), 5,065 had rheumatic or autoimmune diseases, of which 107 individuals were diagnosed with coccidioidomycosis during the study period (6.1 per 1,000 person-years). Increased risk of coccidioidomycosis was observed among beneficiaries prescribed any BRMs (17.7 per 1,000 person-years; adjusted hazard ratio [aHR] 3.94; 95% confidence interval [CI] 1.18-13.16), followed by individuals treated with only corticosteroids (12.2 per 1,000 person-years; aHR 2.29; 95% CI 1.05-5.03) compared to those treated with only OSMs (4.2 per 1,000 person-years). The rate of those treated with only OSMs was the same as that of beneficiaries without these medications. Incidence of coccidioidomycosis was low among 2011 to 2016 Medicare beneficiaries with rheumatic or autoimmune diseases. BRM and corticosteroid users may have higher risks of coccidioidomycosis compared to nonusers, warranting consideration of screening for patients on BRMs and corticosteroids in coccidioidomycosis endemic areas.

Medication use and risk of amyotrophic lateral sclerosis: using machine learning for an exposome-wide screen of a large clinical database

Background Accumulating evidence suggests that non-genetic factors have important etiologic roles in amyotrophic lateral sclerosis (ALS), yet identification of specific culprit factors has been challenging. Many medications target biological pathways implicated in ALS pathogenesis, and screening large pharmacologic datasets for signals could greatly accelerate the identification of risk-modulating pharmacologic factors for ALS. Method We conducted a high-dimensional screening of patients’ history of medication use and ALS risk using an advanced machine learning approach based on gradient-boosted decision trees coupled with Bayesian model optimization and repeated data sampling. Clinical and medication dispensing data were obtained from a large Israeli health fund for 501 ALS cases and 4,998 matched controls using a lag period of 3 or 5 years prior to ALS diagnosis for ascertaining medication exposure. Results Of over 1,000 different medication classes, we identified 8 classes that were consistently associated with increased ALS risk across independently trained models, where most are indicated for control of symptoms implicated in ALS. Some suggestive protective effects were also observed, notably for vitamin E. Discussion Our results indicate that use of certain medications well before the typically recognized prodromal period was associated with ALS risk. This could result because these medications increase ALS risk or could indicate that ALS symptoms can manifest well before suggested prodromal periods. The results also provide further evidence that vitamin E may be a protective factor for ALS. Targeted studies should be performed to elucidate the possible pathophysiological mechanisms while providing insights for therapeutics design.

예측과정을 이용한 연령별 시차 분포 모형

Interest in mental disease is increasing. Recently a positive association between elevated temperature and mental disease has been reported. However, there was a limitation in that detailed interaction with age could not be confirmed. In this study, to overcome such limitations, the association between emergency room visits due to mental disease and mean temperature was explored by using the age-specific distributed lag model. The age-specific distributed lag model is a model in which a coefficient of age and lagged temperature are integrated into the existing distributed lag model. Accordingly the dimension of the parameter space was reduced by expressing the increased parameters as a linear combination of prediction process basis functions and the accuracy of parameter estimation was increased using information on the total age. The degree of borrowing information over age was estimated through variogram modeling. From 2014 to 2020, 906,958 patients visited the emergency room due to mental disease in Seoul. The age groups with a positive cumulative association over the lag period of 0-3 days between mean temperature and emergency room visits due to mental disease were 15 to 24, 40 to 59 and 80 to 84. As the effects of climate change become a reality, understanding detailed vulnerabilities will become very important for public health planning and intervention.

Phosphodiesterase Type 5 Inhibitors in Men With Erectile Dysfunction and the Risk of Alzheimer Disease: A Cohort Study.

Repurposing phosphodiesterase type 5 inhibitors (PDE5Is) as drugs for Alzheimer disease (AD) risk reduction has shown promise based on animal studies. However, evidence in humans remains inconclusive. Therefore, we conducted a cohort study to evaluate the association between PDE5I initiation compared with nonuse and the risk of developing AD in men with erectile dysfunction (ED). Using electronic health records from IQVIA Medical Research Data UK (formerly known as the THIN database), we identified men aged ≥40 years with a new diagnosis of ED between 2000 and 2017. Individuals with a previous diagnosis of dementia, cognitive impairment, confusion, or prescription for dementia symptoms were excluded. The occurrence of incident AD was identified using diagnostic read codes. To minimize immortal-time bias, PDE5I initiation was treated as a time-varying exposure variable. Potential confounders were adjusted using inverse probability of treatment weighting based on propensity scores. Cox proportional hazard models were used to estimate the adjusted hazard ratio (HR) with 95% CIs. A secondary analysis explored the association between AD and the cumulative number of PDE5I prescriptions. Sensitivity analyses included lag (delay) periods of 1 and 3 years after cohort entry to address the prodromal stage of AD. The study included 269,725 men, with 1,119 newly diagnosed with AD during a median follow-up of 5.1 (interquartile range 2.9-8.9) years. The adjusted HR in PDE5I initiators compared with nonuse was 0.82 (95% CI 0.72-0.93). The associated risk of AD decreased in individuals issued >20 prescriptions: HR 0.56 (95% CI 0.43-0.73) for 21-50 prescriptions and HR 0.65 (95% CI 0.49-0.87) for >50 prescriptions. Sensitivity analysis with a 1-year lag period supported the primary findings (HR 0.82, 95% CI 0.72-0.94), but the results differed with the inclusion of a 3-year lag period (HR 0.93, 95% CI 0.80-1.08). PDE5I initiation in men with ED was associated with a lower risk of AD, particularly in those most frequently issued prescriptions. The differences between primary and sensitivity analyses highlight the need to explore the optimal lag period. To enhance the generalizability of our findings, a randomized controlled trial including both sexes and exploring various PDE5I doses would be beneficial to confirm the association between PDE5I and AD.

Invading plants remain undetected in a lag phase while they explore suitable climates.

Successful alien species may experience a period of quiescence, known as the lag phase, before becoming invasive and widespread. The existence of lags introduces severe uncertainty in risk analyses of aliens as the present state of species is a poor predictor of future distributions, invasion success and impact. Predicting a species' ability to invade and pose negative impacts requires a quantitative understanding of the commonality and magnitude of lags, environmental factors and mechanisms likely to terminate lag. Using herbarium and climate data, we analysed over 5,700 time series (species × regions) in 3,505 naturalized plant species from nine regions in temperate and tropical climates to quantify lags and test whether there have been shifts in the species' climatic space during the transition from the lag phase to the expansion phase. Lags were identified in 35% of the assessed invasion events. We detected phylogenetic signals for lag phases in temperate climate regions and that annual self-fertilizing species were less likely to experience lags. Where lags existed, they had an average length of 40 years and a maximum of 320 years. Lengthy lags (>100 years) were more likely to occur in perennial plants and less frequent in self-pollinating species. For 98% of the species with a lag phase, the climate spaces sampled during the lag period differed from those in the expansion phase based on the assessment of centroid shifts or degree of climate space overlap. Our results highlight the importance of functional traits for the onset of the expansion phase and suggest that climate discovery may play a role in terminating the lag phase. However, other possibilities, such as sampling issues and climate niche shifts, cannot be ruled out.

(083) The Association of Urinary Tract Infections with Anti-Androgen Medications: A Claims Database Analysis

Abstract Introduction Urinary tract infections (UTI) are highly prevalent among women, with 27% having recurrence within six months. While initial antibiotic treatment resolves symptoms for a subset of women; 20-40% experience symptom recurrence. Recent work has identified androgen receptors in the vestibule and vaginal mucosa, and the correlation between androgen deficiency and hormonally mediated vestibulodynia (HMV), frequently misdiagnosed as UTI, is widely accepted as a potential pathophysiological mechanism. Objective We sought to characterize rates of UTIs with anti-androgen medications utilizing a national claims database. Methods The TriNetX database was queried from May 2023 with selection criteria based on ICD-10 codes (Figure 1). The primary study outcome was a risk of UTI after anti-androgen medication within 2 weeks to 1-year from at least 3 anti-androgen medication prescriptions. We defined a 2-week lag period after the last medication prescription based on the assumption that UTI diagnosed immediately after an anti-androgen medication prescription was likely due to factors other than the medication. Moreover, other medications prescribed for UTIs were not included in the analysis due to their indication for various infections in addition to UTIs. Recurrent UTI (rUTI) was defined as greater than 2 diagnoses of UTI within 2-weeks to 6-months, or greater than 3 diagnoses of UTI within 2-weeks to 1-year of medication prescription. Results Our query identified 418,117 females aged 18 – 51 years with at least 3 anti-androgen prescriptions in the last 5 years; 209,669 females had 3-6 prescriptions; 94,193 females had 7-10 prescriptions; 45,624 females had 11-14 prescriptions; and 61,941 females had ≥ 15 prescriptions. Risk of UTI between two weeks-1 year after anti-androgen prescriptions was significantly higher compared to propensity-score matched controls (13.2% vs 10.2%; Risk Ratio (RR) 1.3, 95% Confidence Interval (CI) [1.28 – 1.32]). Significant difference in UTI-free survival was observed between the two groups (Hazard ration (HR) = 1.10, 95% CI [1.09 – 1.12]) (Figure 2). Compared to those with 3-6 prescriptions, propensity-score matched groups of those with 7-10, 11-14, or ≥ 15 prescriptions had significantly lower RR of UTIs within 2-weeks to 1-year from prescriptions (RR 7-10 vs 3-6 0.91, 95% CI [0.88-0.94]; RR 11-14 vs 3-6 0.90 [0.86-0.95]; RR ≥ 15 vs 3-6 0.88 [0.85-0.91]) (Figure 3). RR of UTI within 2-weeks to 1-year from prescriptions was comparable between propensity-score matched groups of 7-10, 11-14, and ≥ 15 prescriptions (RR 11-14 vs 7-10 1.03, 95% CI [0.98-1.08]; RR ≥ 15 vs 7-10 0.97, 95% CI [0.94-1.01]; RR ≥ 15 vs 11-14 0.96, 95% CI [0.91-1.01]). Conclusions The risk of UTI is notably higher with the use of anti-androgen medications. Further clinical studies are needed to further elucidate this correlation with the goal of including vulvar physiology and vulvar conditions in the diagnostic work up of recurrent UTIs. Disclosure No.

Glomus Tumors: A Systematic Review of the Sub-Saharan Africa Experience.

Glomus tumors are rare benign tumors that were first described in 1812 by Wood. They arise from normal glomus apparatus, usually located in the reticular dermis of the body. Although glomus tumors are universal in occurrence, the sub-Saharan Africa experience has not been well documented. The authors performed a systematic literature review of eligible studies between 1960 and August 2023, using the terms "glomus," "tumor," "glomangioma," "glomangiomyoma," and "Africa." We also performed a search of the AIC Kijabe Hospital pathology department database of about 140,000 records, covering 30 years, for the terms "glomus tumor," "glomangioma" and "glomangiomyoma." The systematic literature search and institutional database search produced a total of 74 patients who had glomus tumors. These patients had a lag of between 3 months and 20 years from symptom development to definitive treatment. There are very few reports of glomus tumors from sub-Saharan Africa in the current literature: the authors' histopathology database of 140,000 specimens had 46 glomus tumors (0.03%), and only 28 additional patients were found in literature from sub-Saharan Africa. The low numbers of African patients may indicate racial differences in the occurrence of glomus tumors, although this may also be due to failure of clinicians to recognize glomus tumors. The prolonged lag period between symptom development and definitive treatment for glomus tumors indicates the need for diligence in the diagnosis and treatment of a simple problem that is otherwise the cause of incapacitating pain and misery.

Herpes zoster diagnosis and treatment in relation to incident dementia: A population-based retrospective matched cohort study.

Evidence suggests that some infectious diseases, such as herpes zoster (HZ), are associated with elevated risk of subsequent dementia, while certain anti-viral medications are associated with lower risk. We sought to evaluate associations between HZ diagnosis and treatment with incident dementia in a large, retrospective matched cohort. Using ICD-9 and ICD-10 diagnosis codes in electronic medical records, we identified members of Kaiser Permanente Northwest age 50 and older from 2000-2019 with a HZ diagnosis during this period. A comparison group without HZ diagnosis was individually matched 3:1 on age at HZ diagnosis date (index date), sex, and membership length prior to index date. We excluded subjects with dementia diagnosed before the index date. Antiherpetic medication was identified using pharmacy fills 1 month before to 12 months after the index date. We employed survival analysis to examine the associations between dementia and HZ diagnosis and antiherpetic medication, adjusting multivariable models for demographic and clinical factors. We stratified on age and sex and conducted a sensitivity analysis with a 5-year lag period. The study included 101,328 persons, 25,332 with HZ. Over a median follow-up of 4.8 years, 6,000 developed dementia. HZ diagnosis was not associated with higher hazard of dementia (hazard ratio (HR) = 0.99, 95% CI 0.93-1.05) in the primary analysis. Among persons with HZ diagnoses, the HR for receipt of any antiherpetic medication was 0.79 (95% CI 0.70-0.90) in univariate analysis and 0.88 (95% CI 0.77-1.00) after adjustment for demographic and clinical factors. Dementia was not associated with trends in duration of medication use or cumulative dose. We found little evidence for an association between HZ diagnosis and dementia overall. Antiherpetic medication prescribed around the time of HZ diagnosis was statistically associated with lower risk of subsequent dementia in some but not all analyses and subgroups.

P672 Occurrence of malignancy among infliximab biosimilar and bio-originator initiators in Canada: a comparative population-based analysis

Abstract Background Infliximab (INF) downregulates the immune system. Given the immune system's role in deleting pre-cancerous cells, malignancy is a potential concern. Still, relatively few real-world data analyses have compared biosimilar versus bio-originator INF in terms of malignancy incidence. We aimed to compare malignancy occurrence among initiators of infliximab biosimilar (INF-B) and originator (INF-O). Methods We used data from the National Prescription Drug Utilization Information System (NPDUIS), containing pan-Canadian (except Quebec) claims-level data on prescription dispensations paid from public drug programs linked to comprehensive day surgery and inpatient care (Discharge Abstract Database, DAD) and hospital-based and community-based ambulatory care (National Ambulatory Care Reporting System, NACRS). We studied adults (≥18 years) initiating INF between January 2015 and December 2019 with no history of malignancy, HIV or organ transplant (1-year pre-baseline). Follow-up began 365 days after treatment initiation (lag period) and continued until the first cancer diagnostic code (ICD-10 C00-C97), treatment discontinuation + 365 days, or end of study period. We compared INF-B and INF-O using Cox regression models, adjusting for potential confounders/ effect modifiers: sex, age at treatment initiation, prior use of other biologics or prednisone, province (Ontario versus others), and calendar year. Results New users of INF-B (2,019) and INF-O (5,183) were about half female (52%), with a median age (interquartile range) of 45 years (28-62). Overall, the malignancy incidence rate was 10.2 (95% confidence interval, CI, 8.7-11.8) events per 1,000 person-years. Comparing INF-B to INF-O, the adjusted hazard ratio for malignancy was 0.97 (95% CI 0.63-1.48). Conclusion In this real-world dataset, we were unable to identify clear differences in malignancy comparing INF-B and INF-O. Limitations include the inability to control for residual confounders (e.g., disease severity), potential outcome misclassification, and selection bias.

P1166 Thiopurines and Risk of Cancer in Patients with Inflammatory Bowel Disease -A Danish Nationwide Cohort study 1996-2018

Abstract Background Thiopurines are frequently used in patients with inflammatory bowel disease (IBD). The aim of this study was to assess the cancer risk of thiopurine monotherapy and thiopurine in combination with biologics compared to unexposed IBD patients. Methods Incident Danish IBD patients from 1996 to 2018 were identified in the national registers. Time at risk started at the date of IBD diagnosis and exposure status was time-dependent. Exposure was defined as registration of thiopurine and/or biologics. A lag period of 6 months was introduced at the first thiopurine registration as it was unlikely to have caused an effect on any immediate cancer case. If no new registration of thiopurines occurred 6 months from the last registration, the patient was assigned to the discontinued group. Non-melanoma skin cancer was analysed separately to avoid masking severe cancer forms and excluded from the overall cancer analyses. Cox regressions were performed to assess the risk of first cancer and risk estimates were presented as hazard ratios (HR) with 95% confidence intervals (CI). Only the incidence bar plot included non-IBD controls, matched on age, sex and municipality. Controls were unexposed to thiopurines. Results In total, 43,404 IBD patients were followed for a median of 8.2 years (IQR:3.7-14.2) from diagnosis. During follow-up, 7,736 Crohn’s disease (CD) (50.6%) and 6,632 ulcerative colitis (UC) patients (23.6%) were exposed to thiopurines. Cancer occurred in 1,292 (8.4%) CD and 1,840 (6.5%) UC patients. Both monotherapy and combination therapy were associated with developing any cancer (HR: 1.61 (95%CI:1.42-1.84) and (HR: 3.15 (95%CI:2.10-4.73), respectively) compared to unexposed IBD patients. In the elderly (>65 years), this was particularly apparent (Figure 1). The association between cancer and thiopurines was observed in non-melanoma skin-, melanoma-, urinary tract-, female genital organ-, lymphoid tissue-, colorectal- and digestive organ cancers. In patients who discontinued thiopurines, the HR returned to the level of unexposed HR: 1.01 (95%CI:0.91-1.13). The association with different cancer forms were higher in patients with >4 years and 1-4 years of thiopurine exposure, HR 1.58 (95%CI:1.37-1.82) and HR 1.24 (95%CI:1.07-1.44), compared to unexposed. Conclusion Thiopurines were associated with an increased risk of cancer in both mono- and combination therapy, especially in the elderly. This was noticeable in patients with 1-4 and >4 years of exposure, with 24% and 58% increased risk compared to unexposed. Reassuringly, discontinuation of thiopurines returned the risk to baseline and the absolute number of cancers was low. This warrants closer monitoring of all IBD patients, especially the elderly in combination therapy.

Assessing the importance of primary care diagnoses in the UK Biobank

The UK Biobank has made general practitioner (GP) data (censoring date 2016–2017) available for approximately 45% of the cohort, whilst hospital inpatient and death registry (referred to as “HES/Death”) data are available cohort-wide through 2018–2022 depending on whether the data comes from England, Wales or Scotland. We assessed the importance of case ascertainment via different data sources in UKB for three diseases that are usually first diagnosed in primary care: Parkinson’s disease (PD), type 2 diabetes (T2D), and all-cause dementia. Including GP data at least doubled the number of incident cases in the subset of the cohort with primary care data (e.g. from 619 to 1390 for dementia). Among the 786 dementia cases that were only captured in the GP data before the GP censoring date, only 421 (54%) were subsequently recorded in HES. Therefore, estimates of the absolute incidence or risk-stratified incidence are misleadingly low when based only on the HES/Death data. For incident cases present in both HES/Death and GP data during the full follow-up period (i.e. until the HES censoring date), the median time difference between an incident diagnosis of dementia being recorded in GP and HES/Death was 2.25 years (i.e. recorded 2.25 years earlier in the GP records). Similar lag periods were also observed for PD (median 2.31 years earlier) and T2D (median 2.82 years earlier). For participants with an incident GP diagnosis, only 65.6% of dementia cases, 69.0% of PD cases, and 58.5% of T2D cases had their diagnosis recorded in HES/Death within 7 years since GP diagnosis. The effect estimates (hazard ratios, HR) of established risk factors for the three health outcomes mostly remain in the same direction and with a similar strength of association when cases are ascertained either using HES only or further adding GP data. The confidence intervals of the HR became narrower when adding GP data, due to the increased statistical power from the additional cases. In conclusion, it is desirable to extend both the coverage and follow-up period of GP data to allow researchers to maximise case ascertainment of chronic health conditions in the UK.

Trends in private caregiving cost after implementing a comprehensive nursing service covered by national health insurance: Interrupted time series

BackgroundThe Korean government has implemented a comprehensive nursing care service system (CNS) to mitigate the stress faced by caregivers. ObjectiveThis study aimed to assess trends in the estimated average costs of private caregiving and determine the difference in costs between those using CNS and those not using it. DesignA comparative interrupted time series analysis with a 2-year lag period verified total private caregiving cost trends; biannual differences in costs were evaluated based on using CNS. ParticipantsThe main unit of analysis was episode. We extracted a total of 6418 episodes of hospitalization in acute care settings that included the use of caregiving services (formal, informal caregiving and CNS). MethodsWe conducted segmented regression to assess the impact of CNS on total private caregiving costs using data from 2012 to 2018, excluding the years 2015 and 2016 of the Korean Health Panel dataset. ResultsWe presented that the immediate mean difference in total private caregiving costs between CNS users and non-users was −444.7 USD two years after the implementation of the CNS policy (95 % CI −714.5 to −174.5, p-value 0.001). Among individuals living in rural areas, two years after the implementation of the CNS policy, there was a significant immediate mean cost difference of −476.9 USD in total private caregiving costs between CNS users and non-users (p-value 0.011). Similarly, for episodes with a Charlson Comorbidity Index (CCI) score of 0 to 1, there was a substantial immediate mean cost difference in total private caregiving costs between CNS users and non-users, amounting to −399.9 USD two years after the CNS policy (p-value 0.008). ConclusionsThis study evaluated the trend of total private caregiving costs between groups using and not using CNS. After two years of being covered by CNS health insurance, those who utilized CNS paid $433 less for their total private caregiving cost over a 6-month period, compared to those who did not use CNS. The adoption of CNS may be an effective system for relieving the financial burden on inpatients in need of private caregiving services. Tweetable abstractKorean Comprehensive Nursing Service reduces private caregiving costs

Empirical Analysis of the Predicting Future Trend in Nasdaq Using ARIMA Model

The paper delves into a detailed empirical analysis leveraging the ARIMA model, with data gleaned from the weekly return trends of the Nasdaq Index. Using diagnostic tools such as ACF, PACF, and the AIC information criteria, the study zeroes in on the optimal lag period for the model. Subsequently, this refined model is employed to forecast potential trajectories for the Nasdaq Index's weekly returns. Through a thorough examination of analytical outcomes, especially AIC values, the study gauges the margin of prediction errors, culminating in the selection of the most proficient forecasting model: ARIMA (2,0,2). Importantly, these analytical insights serve as a valuable compass for investors aiming to capitalize on lucrative opportunities or mitigate potential risks within the Nasdaq stock exchange. Furthermore, it underscores the importance of empirical data analysis in guiding informed decision-making, ensuring optimal returns in the volatile Nasdaq market landscape. This work acts as a beacon for those navigating the intricate nuances of stock market investments.

Chukotka as a Portal for the Rabies Introduction into Kamchatka (Systematic Review)

The aim of this review was to assess the peculiarities of distribution and epidemiological risk of rabies in the extreme northeast of Asia. The systematic review was prepared through synthesizing publications on rabies over 1860–2022 (n=22) and previously unpublished data for 2009–2023. From the late 19th century until the 1980s, rabies epizootics were consistently observed in Chukotka and Kamchatka. A correlation was found between the time of occurrence of rabies in those territories with a lag period of 1–2 years (r=0.349; p=0.054). In 2009–2023, 24 animal rabies cases were confirmed in Chukotka; rabies has not been registered in Kamchatka since 1981. Until 1982, 5 confirmed human rabies cases were described in Chukotka, as well as 4 lethal cases presumably due to rabies (Chukotka – 3, Kamchatka – 1). The similarity of the spatial distribution of epizootics in different periods of time was established. Rabies was detected mainly in the area of the permanent polar fox (Vulpes lagopus) habitation, in the coastal tundra from the mouth of the Kolyma River to the Anadyr Gulf. Outside this territory (the valleys of the Anadyr and Penzhina Rivers, the Kamchatka Peninsula), rabies was reported in red foxes (Vulpes vulpes). At present, the importance of the polar fox in the spread of rabies in Chukotka has decreased, while the significance of the red fox has increased substantially. Due to vaccination, rabies among dogs is recorded sporadically. Rabies virus isolates from Chukotka belong to the Arctic genetic lineage (Arctic-3 group), which has a circumpolar distribution. The possibility of independent circulation of the rabies virus in the Kamchatka Peninsula is doubtful because of the limited size of the red fox population. Based on the mapping, possible directions for the introduction of rabies to Kamchatka from Chukotka have been identified. Barrier oral rabies vaccination of foxes is recommended during the years of high abundance of red and polar foxes in Chukotka.

Hysteresis analysis reveals how phytoplankton assemblage shifts with the nutrient dynamics during and between precipitation patterns

The escalation of global eutrophication has significantly increased due to the impact of climate change, particularly the increased frequency of extreme rainfall events. Predicting and managing eutrophication requires understanding the consequences of precipitation events on algal dynamics. Here, we assessed the influence of precipitation events throughout the year on nutrient and phytoplankton dynamics in a drinking water reservoir from January 2020 to January 2022. Four distinct precipitation patterns, namely early spring flood rain (THX), Plum rain (MY), Typhoon rain (TF), and Dry season (DS), were identified based on rainfall intensity, duration time, and cumulative rainfall. The study findings indicate that rainfall is the primary driver of algal dynamics by altering nutrient levels and TN:TP ratios during wet seasons, while water temperature becomes more critical during the Dry season. Combining precipitation characteristics with the lag periods between algal proliferation and rainfall occurrence is essential for accurately assessing the impact of rainfall on algal blooms. The highest algae proliferation occurred approximately 20 and 30 days after the peak rainfall during the MY and DS periods, respectively. This was influenced by the intensity and cumulative precipitation. The reservoir exhibited two distinct TN/TP ratio stages, with average values of 52 and 19, respectively. These stages were determined by various forms of nitrogen and phosphorus in rainfall-driven inflows and were associated with shifts from Bacillariophyta-dominated to Cyanophyta-dominated blooms during the MY and DS seasons. Our findings underscore the interconnected effects of nutrients, temperature, and hydrological conditions driven by diverse rainfall patterns in shaping algal dynamics. This study provides valuable insights into forecasting algal bloom risks in the context of climate change and developing sustainable strategies for lake or reservoir restoration.

The unexpected effect of the compound microbial agent NP-M2 on microbial community dynamics in a nonylphenol-contaminated soil: the self-stability of soil ecosystem.

Nonylphenol (NP) is widely recognized as a crucial environmental endocrine-disrupting chemical and persistent toxic substance. The remediation of NP-contaminated sites primarily relies on biological degradation. Compound microbial products, as opposed to pure strains, possess a greater variety of metabolic pathways and can thrive in a wider range of environmental conditions. This characteristic is believed to facilitate the synergistic degradation of pollutants. Limited research has been conducted to thoroughly examine the potential compatibility of compound microbial agents with indigenous microflora, their ability to function effectively in practical environments, their capacity to enhance the dissipation of NP, and their potential to improve soil physicochemical and biological characteristics. In order to efficiently eliminate NP in contaminated soil in an eco-friendly manner, a simulation study was conducted to investigate the impact of bioaugmentation using the functional compound microbial agent NP-M2 at varying concentrations (50 and 200 mg/L) on the dynamics of the soil microbial community. The treatments were set as follows: sterilized soil with 50 mg/kg NP (CK50) or 200 mg/kg NP (CK200); non-sterilized soil with 50 mg/kg NP (TU50) or 200 mg/kg NP (TU200); non-sterilized soil with the compound microbial agent NP-M2 at 50 mg/kg NP (J50) or 200 mg/kg NP (J200). Full-length 16S rRNA analysis was performed using the PacBio Sequel II platform. Both the indigenous microbes (TU50 and TU200 treatments) and the application of NP-M2 (J50 and J200 treatments) exhibited rapid NP removal, with removal rates ranging from 93% to 99%. The application of NP-M2 further accelerated the degradation rate of NP for a subtle lag period. Although the different treatments had minimal impacts on the soil bacterial α-diversity, they significantly altered the β-diversity and composition of the bacterial community. The dominant phyla were Proteobacteria (35.54%-44.14%), Acidobacteria (13.55%-17.07%), Planctomycetes (10.78%-11.42%), Bacteroidetes (5.60%-10.74%), and Actinobacteria (6.44%-8.68%). The core species were Luteitalea_pratensis, Pyrinomonas_methylaliphatogenes, Fimbriiglobus_ruber, Longimicrobium_terrae, and Massilia_sp003590855. The bacterial community structure and taxon distribution in polluted soils were significantly influenced by the activities of soil catalase, sucrase, and polyphenol oxidase, which were identified as the major environmental factors. Notably, the concentration of NP and, to a lesser extent, the compound microbial agent NP-M2 were found to cause major shifts in the bacterial community. This study highlights the importance of conducting bioremediation experiments in conjunction with microbiome assessment to better understand the impact of bioaugmentation/biostimulation on the potential functions of complex microbial communities present in contaminated soils, which is essential for bioremediation success.