Liquefaction resistance of fibre-reinforced silty sands under cyclic loading

Whether the so-called double porosity in soils with a loose and natural packing state is a concept with real-world implications is a fundamental yet controversial question in the study of cyclic undrained shear behaviour of fibre-reinforced silty sands. An attempt is made here to clarify the question by means of particle-level modelling combined with 41 undrained cyclic triaxial shear tests. The study shows that the initial Random Loose Packing changes to Random Close Packing and then Close Packing with silt content increments. The transition from random to close packing occurs at a threshold silt content which is relatively lower in coarser sands. For sands with 40% silt content. Irrespective of fine content, fibres tend to sit deep into the silt pellets and encrust the macro-pore spaces. Generally, increasing fibre content leads to an increase in the average number of contacts per particle, dilation and easier dissipation of excess pore water pressure, a decrease in contact forces and improved liquefaction resistance. For sands with >40% silt content, effectiveness of fibre reinforcement diminishes with increasing sand median size

Exploring the interplay between the clinical and presumed effect of botulinum injections for cervical dystonia: a pilot study

BACKGROUND: Repetitive intramuscular injections of botulinum neurotoxin type A (BoNT/A) are the treatment of choice in patients with cervical dystonia (CD). As soon as BoNT therapy is initiated, the natural course of CD cannot be observed anymore. Nevertheless, the present study focuses on the "presumed" course of disease severity under the assumption that no BoNT therapy had been performed. The "experienced" benefit is compared with the "presumed" worsening. METHODS: Twenty-seven BoNT/A long-term-treated CD patients were recruited. They had to assess the remaining severity of CD in percent of its severity at the start of BoNT therapy (RS-%). Then, they had to draw the course of severity from the onset of symptoms to the start of BoNT/A therapy (CoDB graph), as well as the course of severity from the start of BoNT/A therapy until the day of recruitment (CoDA graph). Then, they were instructed to presume the development of CD severity from the day of the start of BoNT/A therapy until the day of recruitment under the assumption that no BoNT/A therapy had been performed, and to assess the maximal severity they could presume in percent of the severity at the start of BoNT therapy (IS-%). Then, they had to draw the "presumed" development of CD severity (CoDI graph). The "experienced" change in disease severity and the "presumed" change since the start of BoNT/A therapy were compared and correlated with a variety of demographical and treatment-related data, including the actual severity of CD at the day of recruitment, which was assessed using the TSUI score and the actual dose per session (ADOSE). RESULTS: No CD patients expected an improvement without BoNT therapy. "Presumed" worsening ((IS-%)-100) was about 50% in the mean and did not correlate with the "experienced" benefit (100-(RS-%)). However, IS-% was significantly correlated with ATSUI and ADOSE. CONCLUSION: Obviously, CD patients have the opinion that their CD would have further progressed and worsened if no BoNT/A therapy had been performed. Thus, the total benefit of BoNT/A therapy for a patient with CD is a combination of the "experienced" benefit under BoNT/A therapy and the prevented worsening of CD that the patient expects to occur without BoNT/A therapy

"Pseudo"-secondary treatment failure explained via disease progression and effective botulinum toxin therapy: a pilot simulation study

BACKGROUND: The objective of this study was to provide evidence from a simple simulation. In patients with focal dystonia, an initial good response to botulinum neurotoxin (BoNT) injections followed by a secondary worsening does not necessarily arise from an antibody-induced secondary treatment failure (NAB-STF), but may stem from a "pseudo"-secondary treatment failure (PSEUDO-STF). METHODS: The simulation of the outcome after BoNT long-term treatment was performed in four steps: 1. The effect of the first single BoNT injection (SI curve) was displayed as a 12-point graph, corresponding to the mean improvement from weeks 1 to 12. 2. The remaining severity of the dystonia during the nth injection cycle was calculated by subtracting the SI curve (weighted by the outcome after n - 1 cycles) from the outcome after week 12 of the (n - 1)th cycle. 3. A graph was chosen (the PRO curve), which represents the progression of the severity of the underlying disease during BoNT therapy. 4. The interaction between the outcome during the nth BoNT cycle and the PRO curve was determined. RESULTS: When the long-term outcome after n cycles of BoNT injections (applied every 3 months) was simulated as an interactive process, subtracting the effect of the first cycle (weighted by the outcome after n - 1 cycles) and adding the progression of the disease, an initial good improvement followed by secondary worsening results. This long-term outcome depends on the steepness of the progression and the duration of action of the first injection cycle. We termed this response behavior a "pseudo"-secondary treatment failure, as it can be compensated via a dose increase. CONCLUSION: A secondary worsening following an initial good response in BoNT therapy of focal dystonia might not necessarily indicate neutralizing antibody induction but could stem from a "PSEUDO"-STF (a combination of good response behavior and progression of the underlying disease). Thus, an adequate dose adaptation must be conducted before diagnosing a secondary treatment failure in the strict sense

Safety and discontinuation rate of dimethyl fumarate (Zadiva®) in patients with multiple sclerosis: an observational retrospective study

BACKGROUND: This study evaluates the real-world safety and discontinuation rate of Zadiva® (generic product of dimethyl fumarate (DMF)) in Iranian patients with relapsing-remitting multiple sclerosis (RRMS), supplementing existing clinical evidence from randomized controlled trials. METHODS: This retrospective observational study evaluated the real-world safety and discontinuation rate of DMF in RRMS patients from Amir A'lam referral hospital's neurology clinic. Data on safety, discontinuation rate, and clinical disease activity were collected retrospectively. The study aimed to assess the discontinuation rate, safety, and reasons for discontinuation, as well as the number of patients experiencing a relapse, MRI activity, and EDSS scores. RESULTS: In total, 142 RRMS patients receiving DMF were included in the study, with 15 discontinuing treatment due to adverse events, lack of efficacy, or pregnancy. Notably, a significant reduction in relapse rates was observed, with 90.8% of patients remaining relapse-free throughout the study period. After 1 year of treatment with Zadiva®, only 17.6% of patients experienced MRI activity, whereas the EDSS score remained stable. CONCLUSIONS: This study provides important real-world data on the safety and tolerability of Zadiva® in RRMS patients. The results indicate that Zadiva® is generally well tolerated and safe, with a low discontinuation rate due to adverse events or lack of efficacy. These findings suggest that Zadiva® is an effective and safe treatment option for RRMS patients in real-world practice

Lessons about botulinum toxin A therapy from cervical dystonia patients drawing the course of disease: a pilot study

AIM OF THE STUDY: To compare the course of severity of cervical dystonia (CD) before and after long-term botulinum toxin (BoNT) therapy to detect indicators for a good or poor clinical outcome. PATIENTS AND METHODS: A total of 74 outpatients with idiopathic CD who were continuously treated with BoNT and who had received at least three injections were consecutively recruited. Patients had to draw the course of severity of CD from the onset of symptoms until the onset of BoNT therapy (CoDB graph), and from the onset of BoNT therapy until the day of recruitment (CoDA graph) when they received their last BoNT injection. Mean duration of treatment was 9.6 years. Three main types of CoDB and four main types of CoDA graphs could be distinguished. The demographic and treatment-related data of the patients were extracted from the patients' charts. RESULTS: The best outcome was observed in those patients who had experienced a clear, rapid response in the beginning. These patients had been treated with the lowest doses and with a low number of BoNT preparation switches. The worst outcome was observed in those 17 patients who had drawn a good initial improvement, followed by a secondary worsening. These secondary nonresponders had been treated with the highest initial and actual doses and with frequent BoNT preparation switches. A total of 12 patients were primary nonresponders and did not experience any improvement at all. No relation between the CoDB and CoDA graphs could be detected. Primary and secondary nonresponses were observed for all three CoDB types. The use of initial high doses as a relevant risk factor for the later development of a secondary nonresponse was confirmed. CONCLUSIONS: Patients' drawings of their course of disease severity helps to easily detect "difficult to treat" primary and secondary nonresponders to BoNT on the one hand, but also to detect "golden responders" on the other hand

Pseudocholinesterase as a biomarker for untreated Wilson's disease

The aim of this study was to demonstrate that pseudocholinesterase (CHE) serum level is a useful diagnostic biomarker for untreated Wilson's disease (WD). Between 2013 and 2019, about 75 patients were referred to the outpatient department of the University of Düsseldorf with suspected Wilson's disease. In 31 patients with suspected Wilson's disease (WD-SUS-group), WD was excluded by means of investigations other than analysis of blood and urine. A total of 27 parameters of blood and urine in these 31 patients were compared to those of 20 de novo patients with manifest WD (WD-DEF-group), which parameter showed the highest significance level of difference between the WD-DEF-group and the WD-SUS-group. Thereafter, receiver operating characteristics (ROC-curves) were analyzed to evaluate which parameter showed the largest area under the curve (AUC) to detect WD. Finally, a logistic regression analysis was performed to analyze which combination of parameters allowed the best classification of the 51 patients either into the WD-DEF-group or into the WD-SUS-group. CHE showed the highest significance level for a difference between the WD-DEF- and WD-SUS-group, had the highest AUC, and, in combination with ceruloplasmin, allowed 100% correct classification. Without CHE, no other combination of parameters reached this level of correct classification. After the initiation of treatment, which regularly results in an improvement in CHE, the high diagnostic accuracy of this biomarker was lost. Cholinesterase turns out to be an excellent biomarker for differentiation between untreated de novo patients with manifest WD and heterozygotic gene carriers

Possibility of trout farms efluent return to groundwater In non-agricultural seasons

This project is trying to investigate water contamination after use in ponds. For this aquaculture status, physical and chemical water properties, microbial pollutants and heavy metals levels in the some of trout ponds effluent in East Azerbaijan province were evaluated in 2007 to 2009. The information of groundwater and climate conditions in ten years, Drilling and wells piezometric Information, in local wells are reviewed. According to data obtained from analysis of water samples in the output pools range studied concentrations(term mg/l) some parameters are as follows:(BOD: 1.9-3.2), (COD: 3.4-34.1), (TSS: 26.6-42.7), (N-NO_2:0.003-.136),(P-Po4:0.0170.067), (pH:7.75-8.28). Electrical conductivity (500 ±2 to 1129±144 term µm/cm) in the effluent ponds. Based on the results of we can say that between input and effluent ponds in the review of all factors as chlorine, sulfate, sodium, potassium, total nitrogen, soluble phosphorus, total phosphorus, calcium, total hardness, magnesium, alkalinity and silica significant changes not be observed. Review of water analysis data to some factors (such as: water temperature, EC, pH, NO_2, CO_2, HCO_3, CO_3, DO, COD, BOD) and compare this data with the authorities standard confirmed that the All factors mentioned in effluent is allowed now. In terms of microbial contamination and heavy metals (Zn, Cu, Ca, Pb, Fe, Cr) is no pollution. Appropriate strategies for removing suspended materials must to use. We can use Watershed Management solutions to inject output water to the underground table. Should be noted status change (eg change in flow rate, an unusual increase in temperature, fish density increasing, reducing food quality, lack of appropriate management actions and ...) may reduce the effluent quality and the ability of injection water underground to lose. In this case, measures must be for wastewater treatment and improve the quality ponder

Significantly lower antigenicity of incobotulinumtoxin than abo- or onabotulinumtoxin

BACKGROUND: For many indications, BoNT/A is repetitively injected with the risk of developing neutralizing antibodies (NABs). Therefore, it is important to analyze whether there is a difference in antigenicity between the different licensed BoNT/A preparations. METHODS: In this cross-sectional study, the prevalence of NABs was tested by means of the sensitive mouse hemidiaphragm assay (MHDA) in 645 patients. Patients were split into those having exclusively been treated with the complex protein-free incoBoNT/A preparation (CF-MON group) and those having started BoNT/A therapy with a complex protein-containing BoNT/A preparation (CC-I group). This CC-I group was split into those patients who remained either on abo- or onaBoNT/A (CC-MON group) and those who had been treated with at least two BoNT/A preparations (CC-SWI group). To balance treatment duration, only CC-MON patients who did not start their BoNT/A therapy more than 10 years before recruitment (CC-MON-10 group) were further analyzed. The log-rank test was used to compare the prevalence of NABs in the CF-MON and CC-MON-10 group. RESULTS: In the CF-MON subgroup, no patient developed NABs. In the CC-I group, 84 patients were NAB-positive. NABs were found in 33.3% of those who switched preparations (CC-SWI) and in 5.9% of the CC-MON-10 group. Kaplan-Meier curves for remaining NAB-negative under continuous BoNT/A therapy were significantly different (p < 0.035) between the CF-MON and CC-MON-10 group. CONCLUSION: Frequent injections of a complex protein-containing BoNT/A preparation are associated with significantly higher risks of developing NABs than injections with the same frequency using the complex protein-free incoBoNT/A preparation

A survey on health status of coldwater rearing and hatcheries fish farms in Iran (Mazandarn, Gilan, Ardebil, West Azerbaiejan, East Azerbaiejan and Kordestan provinces)

The national research plan with title of "Study on health status of Iran Coldwater hatchery and rearing farms" was done in order to identification and tracking of main causative agents of recent mortality in Iran Coldwater hatchery and rearing farms and recognize of infected zones and design of landscape distribution of Epizootic Coldwater fish diseases in the country. This plan was conducted parallel and in same time in some polar provinces of Coldwater fish production such as Mazandaran, Gilan, Ardebil, West Azerbaijan, East Azerbaijan and Kurdistan in three years from 2006-2008. In this regard, about 23,21 and 20 farms in Mazandaran province, 30 farms in West and East Azerbaijan and Kurdistan provinces and 19 farms in Gilan and Ardebil were selected as randomly and tracking were done yearly from 2006-2008. This research was conducted according to regular planning consists of farms visit that was done according to statistical plan and completion of Questionnaires and sampling. The findings in Mazandaran province revealed that fish infections background and infectious diseases were increased in period of 2006-2008. In fact, 56% of all fish farms in 2006, 71% in 2007 and 85% in 2008 were recorded as infected farms. In other side, average weight of fish final products was more 500gr in consume market. So, regarding to long period of fish culture in mentioned fish occurrence of more morbidity could be expected. The streptococcus infections were most important fish bacterial diseases that have more incidence and pathogenicity in collected questionnaires. Also it revealed more occurrences in summer season in above 15oC temperature in affected fish farms. Also, Enteric Redmouth Disease (ERM) and Saprolegniasis were reported as second and third degree in examined farms. Meanwhile, findings of control, prevention and treatment of our survey revealed that using of antibiotics and detergent materials were increased in mentioned province. Indeed, 34.7% of all fish farms in 2006, 71.4% in 2007 and 75% in 2008 have applied treatment operation and using of detergent materials in affected farms. In other side, frequent using of Erythromycin antibiotic was reported several times in 2008 so fish farmer faced to Bacterial resistance and should be using from Florfenicol as alternative antibacterial. Also, in feed sampling from all fish farms about 3 fish farms in 2006 and 5 fish farms in 2008 were faced with food poisoning that originated from high TVN and peroxidase in fish food consumed. These farms revealed mass mortality that stopped after change feeding regime. In conclusion absence of fish health management could be considered as main agent of mentioned mortality in Mazandaran province. The findings of our survey in West and East Azerbaijan and Kurdistan revealed that absence of sufficient experiences in fish farmers and their neglect from water quality concepts, farm cleanness, using of suitable detergent materials for fish ponds and instruments and disability in continuous monitoring of physic-chemical factors of consumed water could be considered as most important problems. So, fish morbidity and mortality, growth decrement and low production rate were expected. Unfortunately, despite the occurrence of infectious and non- infectious diseases in examined fish farms, there were no documents and information about diseases history, clinical signs in dead fish, feeding regime, fish mortality (rate of daily mortality, age and weight of moribund fish), treatment operation, drugs usage, growth rate, physico-chemical factors and fish density. So planning for control and prevention of mentioned diseases were unsuccessful in affected fish farms. Also, occurrence of some epizootic fish viral diseases such as VHS, IPN and IHN were observed frequently with mass mortality about 40100% in some examined fish farms that produced some tragic economic lost in the mentioned provinces. Similarly, some bacterial, fungal and parasitic diseases were observed repeatedly in some inspected farms such as Flavobacterium, streptococcus infections. Also, some unknown causative agents in parasitic diseases were observed several times such as Dactylogyrus, Gyrodactylus, Ichthyophthirius multifiliis, Trichodina, Chilodonella, Diplostomum and fungal diseases such as Saprolegniasis. In conclusion it seems that absence of fish health management, inadequate rate of hygienic technical services, absence of quarantine programs for transfer of new eyed-eggs, juvenile and live broodstocks packages without health certificates from authorized organizations, uncontrolled entry of foreign eyed-eggs (France, Denmark, Australia and Armenia) and neglect in using of suitable detergent materials for fish ponds, instruments, consumed water and infected eggs, not screening of broodstocks in hatcheries could be considered as most important causative agents in occurrence of infectious diseases and main problems in affected farms in mentioned provinces. Similarly, our findings in Gilan and Ardebil provinces revealed that their problems were similar to other provinces. In fact, neglect in establish of necessary Infrastructures in fish farms and dereliction in health management concepts could be considered as main reasons of occurrence of fish infectious and non-infectious diseases in studied fish farms in mentioned provinces. In fact, often fish farms visited hadn't suitable structures without control and prevention approach. There were not observed detergent using, quarantine programs and prevention methods. Entrance of unknown persons, birds and wild animals were ordinary in mentioned farms. Unfortunately level of farmer’s knowledge was low and no training courses and extension programs were planned by authorized organizations. Meanwhile, food storages were unsuitable and food packages were stored in inappropriate situation so poisoning conditions were increased in examined farms. In conclusion it could be finalized that Coldwater fish farms in Gilan and Ardebil provinces situated in insufficient position and correction of current situation are needed urgently. In final elicitation, it would be mentioned that lack of basic infrastructures could be introduced as most important reasonfor spread of diseases, mortality and related economic losses in studied provinces. Therefore, attention to environmental affairs and access to Sustainable Development are recommended. Also consideration of biosecurity regulations and health management concepts would be important requirements for modification and reformation of Coldwater fish farms in examined provinces towards A Better Tomorrow

The unfinished agenda of communicable diseases among children and adolescents before the COVID-19 pandemic, 1990-2019: a systematic analysis of the Global Burden of Disease Study 2019

BACKGROUND: Communicable disease control has long been a focus of global health policy. There have been substantial reductions in the burden and mortality of communicable diseases among children younger than 5 years, but we know less about this burden in older children and adolescents, and it is unclear whether current programmes and policies remain aligned with targets for intervention. This knowledge is especially important for policy and programmes in the context of the COVID-19 pandemic. We aimed to use the Global Burden of Disease (GBD) Study 2019 to systematically characterise the burden of communicable diseases across childhood and adolescence. METHODS: In this systematic analysis of the GBD study from 1990 to 2019, all communicable diseases and their manifestations as modelled within GBD 2019 were included, categorised as 16 subgroups of common diseases or presentations. Data were reported for absolute count, prevalence, and incidence across measures of cause-specific mortality (deaths and years of life lost), disability (years lived with disability [YLDs]), and disease burden (disability-adjusted life-years [DALYs]) for children and adolescents aged 0-24 years. Data were reported across the Socio-demographic Index (SDI) and across time (1990-2019), and for 204 countries and territories. For HIV, we reported the mortality-to-incidence ratio (MIR) as a measure of health system performance. FINDINGS: In 2019, there were 3·0 million deaths and 30·0 million years of healthy life lost to disability (as measured by YLDs), corresponding to 288·4 million DALYs from communicable diseases among children and adolescents globally (57·3% of total communicable disease burden across all ages). Over time, there has been a shift in communicable disease burden from young children to older children and adolescents (largely driven by the considerable reductions in children younger than 5 years and slower progress elsewhere), although children younger than 5 years still accounted for most of the communicable disease burden in 2019. Disease burden and mortality were predominantly in low-SDI settings, with high and high-middle SDI settings also having an appreciable burden of communicable disease morbidity (4·0 million YLDs in 2019 alone). Three cause groups (enteric infections, lower-respiratory-tract infections, and malaria) accounted for 59·8% of the global communicable disease burden in children and adolescents, with tuberculosis and HIV both emerging as important causes during adolescence. HIV was the only cause for which disease burden increased over time, particularly in children and adolescents older than 5 years, and especially in females. Excess MIRs for HIV were observed for males aged 15-19 years in low-SDI settings. INTERPRETATION: Our analysis supports continued policy focus on enteric infections and lower-respiratory-tract infections, with orientation to children younger than 5 years in settings of low socioeconomic development. However, efforts should also be targeted to other conditions, particularly HIV, given its increased burden in older children and adolescents. Older children and adolescents also experience a large burden of communicable disease, further highlighting the need for efforts to extend beyond the first 5 years of life. Our analysis also identified substantial morbidity caused by communicable diseases affecting child and adolescent health across the world. FUNDING: The Australian National Health and Medical Research Council Centre for Research Excellence for Driving Investment in Global Adolescent Health and the Bill & Melinda Gates Foundation