Technical Note: Determination of the SCS initial abstraction ratio in an experimental watershed in Greece

International audienceThe present study was conducted in an experimental watershed in Attica, Greece, using observed rainfall/runoff events. The objective of the study was the determination of the initial abstraction ratio of the watershed. The average ratio (Ia/S) of the entire watershed was equal to 0.014. The corresponding ratio at a subwatershed was 0.037. The difference was attributed to the different spatial distribution of landuses and geological formations at the extent of the watershed. Both of the determined ratios are close to the ratio value of 0.05 that has been suggested from many studies for the improvement of the SCS-CN method

Каталітичне карбон-карбон та карбон-гетероатом спряжене приєднання n-заміще- них малеїнімідів до 4н-1,2,4-триазол-3-тіолів, 2-аміно-1,3-тіазолів, 1н-імідазолу та 2-фе- ніліндолізину в присутності кислот льюїса

In the paper the cheap and effective method of the synthesis of 3-heteryl substituted succinimides via catalytic Michael addition are presented. Lewis acids have been found to be effective catalysts for conjugate addition of N-aryl substituted maleimides to the heterocycles with donor-heteroatoms or CH-active function. Catalytic reactions proceed in mild conditions without formation of by-products that are often present in the classical Michael reaction. The compounds synthesized are promising and interesting substrates for biological evaluation since numerous natural products, drugs and drug candidates bear the succinimide core. Moreover, regioselectivity of addition of ambident heterocyclic nucleophiles such as 4H-1,2,4-triazole-3-thiole, 1H-imidazole and 2-amino- 1,3-thiazole to maleimides have been investigated. Lewis acids such as aluminium chloride, zinc chloride and lithium perchlorate have been tested on different heterocyclic substrates as catalysts. Interestingly, depending on nucleophilicity of the substrate different Lewis acids have shown significantly varying efficacy. In this respect aluminium chloride was identified as the most effective catalyst for C–C addition among the Lewis acids tested. Lithium perchlorate appears to be the most efficient in the case of C–N addition with the endocyclic nitrogen atom of the hererocycle. Zinc chloride shows a good catalytic efficacy in addition of maleimides to the exocyclic amino group of 2-aminothiazole. Finally, the advantages of the catalytic approach developed such as mild reaction conditions, easy handling, low toxicity of the catalysts and their low cost make this method useful for the synthesis of new 3-heteryl substituted succinimides, which, in turn, are interesting substrates in medicinal chemistry.В настоящей статье представлен простой и эффективный экономный метод синтеза 3-гетарилзамещенных пирролидин-2,5-дионов с помощью каталитической реакции Михаэля. В качестве катализаторов были использованы кислоты Льюиса, которые показали высокую каталитическую активность в реакциях присоединения N-арилзамещенных малеинимидов к донорным гетероциклам. Представленные реакции протекают в большинстве случаев при комнатной температуре и мягких условиях, что позволяет избегать образования нежелательных побочных продуктов. Синтезированные соединения являются перспективными в области медицинской химии, поскольку хорошо известно, что производные пиролидин-2,5-дионов обладают антибактериальной, антиэпилептической и противотуберкулезной активностью. Также известны продукты природного происхождения, содержащие сукцинимидное ядро, которые являются эффективными и селективными антибиотиками. В представленной работе была исследована региоселективность присоединения малеинимидов к гетероциклическим субстратам. В качестве катализаторов были использованы хлориды алюминия, цинка и перхлорат лития. Оказалось, что апробированные кислоты Льюиса имеют разную каталитическую активность на разных субстратах, что, вероятно, зависит от нуклеофильности гетероцикла. Наиболее эффективным катализатором для С–С присоединения оказался хлорид алюминия, тогда как перхлорат лития показал высокую каталитическую активность при С–N присоединении, а хлорид цинка позволил получить высокие выходы аддуктов в случае присоединения малеинимидов к экзоциклической аминогруппе 2-аминотиазола. Представленный здесь оптимизированный каталитический метод позволяет синтезировать новые 3-гетарилзамещенные пирролидин-2,5-дионы.В даній публікації представлений простий та економний метод синтезу похідних 3-гетерилзаміщених піролідин-2,5-діонів за допомогою каталітичної реакції Міхаеля. В якості каталізаторів були використані кислоти Льюїса, які показали високу каталітичну ефективність у реакціях приєднання N-арилзаміщених малеїнімідів до донорних та СН-активних гетероциклів. Представлені реакції перебігають в основному при кімнатній температурі і м’яких умовах, що дозволяє уникнути утворення небажаних по-бічних продуктів. Синтезовані речовини є цікавими та перспективними об’єктами з точки зору медичної хімії, оскільки відомо, що сполуки із сукцинімідним ядром проявляють антибактеріальну, протитуберкульозну та антиепілептичну активність. Відомі також природні сполуки з піролідин-2,5-діоновим фрагментом, що використовуються як ефективні та селективні антибіотики. У даній роботі було досліджено регіоселективність приєднання малеїнімідів до гетероциклічних субстратів з двома альтернативними донорними центрами. В якості каталізаторів були використані хлориди алюмінію та цинку, а також літію перхлорат. Було виявлено, що випробувані кислоти Льюїса проявляють різну каталітичну активність на різних субстратах, що вочевидь залежить від нуклеофільності гетероциклу. Найбільш ефективним каталізатором для С–С приєднання виявився алюмінію хлорид. У свою чергу, літію перхлорат показав високу каталітичну активність для С–N приєднання, а цинку хлорид був ідентифікований, як найбільш ефективний у випадку приєднання малеїнімідного кільця до екзоциклічної аміногрупи 2-амінотіазолу. Перевагами даного каталітичного методу є м’які реакційні умови, низька токсичність каталізаторів та їх низька ціна, що робить даний підхід синтетично вигідним для отримання 3-гетерилзаміщених піролідин-2,5-діонів

Monte Carlo Deep Neural Network Model for Spread and Peak Prediction of COVID-19

Just a few days before the beginning of this year a new virus, widely known as the COVID-19, was detected in Wuhan, capital of the province Hubei, China. Since then, COVID-19 has spread all across the globe infecting more than half a million people resulting to the passing of nearly 25000 patients. Beside the social pain that this new pandemic is causing, the measures put in force to halt the spreading of the virus are stressing the global economy indicating a domino efect that can last even longer than the probable eradication of COVID-19. Yet, these measures are necessary to prevent health system reach their capacity, an occasion where di cult decisions will need to be made such as prioritization of patients to be treated

Impact of antibiotic timing on mortality from Gram-negative bacteraemia in an English district general hospital: the importance of getting it right every time

Objectives: There is limited evidence that empirical antimicrobials affect patient-oriented outcomes in Gram-negative bacteraemia. We aimed to establish the impact of effective antibiotics at four consecutive timepoints on 30 day all-cause mortality and length of stay in hospital. / Methods: We performed a multivariable survival analysis on 789 patients with Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa bacteraemias. Antibiotic choices at the time of the blood culture (BC), the time of medical clerking and 24 and 48 h post-BC were reviewed. / Results: Patients that received ineffective empirical antibiotics at the time of the BC had higher risk of mortality before 30 days (HR = 1.68, 95% CI = 1.19–2.38, P = 0.004). Mortality was higher if an ineffective antimicrobial was continued by the clerking doctor (HR = 2.73, 95% CI = 1.58–4.73, P < 0.001) or at 24 h from the BC (HR = 1.83, 95% CI = 1.05–3.20, P = 0.033) when compared with patients who received effective therapy throughout. Hospital-onset infections, ‘high inoculum’ infections and elevated C-reactive protein, lactate and Charlson comorbidity index were independent predictors of mortality. Effective initial antibiotics did not statistically significantly reduce length of stay in hospital (−2.98 days, 95% CI = −6.08–0.11, P = 0.058). The primary reasons for incorrect treatment were in vitro antimicrobial resistance (48.6%), initial misdiagnosis of infection source (22.7%) and non-adherence to hospital guidelines (15.7%). / Conclusions: Consecutive prescribing decisions affect mortality from Gram-negative bacteraemia

Long-term outcome and risk factors for late mortality in Gram-negative bacteraemia: a retrospective cohort study

OBJECTIVES: The long-term outcomes of patients following Gram-negative bacteraemia (GNB) are poorly understood. We describe a cohort of patients with GNB over a two-year period and determine factors associated with late mortality (death between days 31 and 365 after detection of bacteraemia). METHODS: This is a single center retrospective observational cohort study of 789 patients with confirmed Escherichia coli, Klebsiella spp and Pseudomonas aeruginosa bacteraemias with a follow-up of one year. Multivariable survival analysis was used to determine the risk factors for late mortality in patients who survived the initial 30-day period of infection. RESULTS: Overall, one-year all-cause mortality was 36.2%, with 18.1% of patients dying within 30 days and 18.1% of patients suffering late mortality. An adverse antimicrobial resistance profile (HR 1.095 per any additional antimicrobial category, 95% CI 1.018 - 1.178, p = 0.014) and infection with Pseudomonas aeruginosa (HR 2.08, 95% CI 1.11 - 3.88, p = 0.022) were independent predictors of late mortality. Other significant factors included the Charlson Comorbidity Index and hospitalization length after the index blood culture. CONCLUSION: Patients with GNB have a poor long-term prognosis. Risk factors for greater mortality at one year include comorbidity, hospitalization length, the infecting organism, and its resistance profile

Post-vaccination COVID-19: A case-control study and genomic analysis of 119 breakthrough infections in partially vaccinated individuals

BACKGROUND: Post-vaccination infections challenge the control of the COVID-19 pandemic. METHODS: We matched 119 cases of post-vaccination SARS-CoV-2 infection with BNT162b2 mRNA, or ChAdOx1 nCOV-19, to 476 unvaccinated patients with COVID-19 (Sept 2020-March 2021), according to age and sex. Differences in 60-day all-cause mortality, hospital admission, and hospital length of stay were evaluated. Phylogenetic, single nucleotide polymorphism (SNP) and minority variant allele (MVA) full genome sequencing analysis was performed. RESULTS: 116/119 cases developed COVID-19 post first vaccination dose (median 14 days, IQR 9 - 24 days). Overall, 13/119 (10∙9%) cases and 158/476 (33∙2%) controls died (p<0.001), corresponding to 4∙5 number needed to treat (NNT). Multivariably, vaccination was associated with 69∙3% (95%CI 45∙8 - 82∙6) relative risk (RR) reduction in mortality. Similar results were seen in subgroup analysis for patients with infection onset ≥14 days after first vaccination (RR reduction 65∙1%, 95%CI 27∙2 - 83∙2, NNT 4∙5), and across vaccine subgroups (BNT162b2: RR reduction 66%, 95%CI 34∙9 - 82∙2, NNT 4∙7, ChAdOx1: RR reduction 78∙4%, 95%CI 30∙4 - 93∙3, NNT 4∙1). Hospital admissions (OR 0∙80, 95%CI 0∙51 - 1∙28), and length of stay (-1∙89 days, 95%CI -4∙57 - 0∙78) were lower for cases, while Ct values were higher (30∙8 versus 28∙8, p = 0.053). B.1.1.7 was the predominant lineage in cases (100/108, 92.6%) and controls (341/446, 76.5%). Genomic analysis identified one post-vaccination case harboring the E484K vaccine escape mutation (B.1.525 lineage). CONCLUSIONS: Previous vaccination reduces mortality when B.1.1.7 is the predominant lineage. No significant lineage-specific genomic changes during phylogenetic, SNP and MVA analysis were detected

Vertical zonation of testate amoebae in the Elatia Mires, northern Greece : palaeoecological evidence for a wetland response to recent climate change or autogenic processes?

The Elatia Mires of northern Greece are unique ecosystems of high conservation value. The mires are climatically marginal and may be sensitive to changing hydroclimate, while northern Greece has experienced a significant increase in aridity since the late twentieth century. To investigate the impact of recent climatic change on the hydrology of the mires, the palaeoecological record was investigated from three near-surface monoliths extracted from two sites. Testate amoebae were analysed as sensitive indicators of hydrology. Results were interpreted using transfer function models to provide quantitative reconstructions of changing water table depth and pH. AMS radiocarbon dates and 210Pb suggest the peats were deposited within the last c. 50 years, but do not allow a secure chronology to be established. Results from all three profiles show a distinct shift towards a more xerophilic community particularly noted by increases in Euglypha species. Transfer function results infer a distinct lowering of water tables in this period. A hydrological response to recent climate change is a tenable hypothesis to explain this change; however other possible explanations include selective test decay, vertical zonation of living amoebae, ombrotrophication and local hydrological change. It is suggested that a peatland response to climatic change is the most probable hypothesis, showing the sensitivity of marginal peatlands to recent climatic change

Inferring from an imprecise Plackett–Luce model : application to label ranking

Learning ranking models is a difficult task, in which data may be scarce and cautious predictions desirable. To address such issues, we explore the extension of the popular parametric probabilistic Plackett–Luce model, often used to model rankings, to the imprecise setting where estimated parameters are set-valued. In particular, we study how to achieve cautious or conservative inference with it, and illustrate their application on label ranking problems, a specific supervised learning task

Synthesis, In Silico, and In Vitro Evaluation of Anti-Leishmanial Activity of Oxadiazoles and Indolizine Containing Compounds Flagged against Anti-Targets

Due to the lack of approved vaccines against human leishmaniasis and the limitations of the current chemotherapy inducing side effects and drug resistance, development of new, effective chemotherapeutic agents is essential. This study describes the synthesis of a series of novel oxadiazoles and indolizine-containing compounds. The compounds were screened in silico using an EIIP/AQVN filter followed by ligand-based virtual screening and molecular docking to parasite arginase. Top hits were further screened versus human arginase and finally against an anti-target battery to tag their possible interactions with proteins essential for the metabolism and clearance of many substances. Eight candidate compounds were selected for further experimental testing. The results show measurable in vitro anti-leishmanial activity for three compounds. One compound with an IC50 value of 2.18 mu M on Leishmania donovani intramacrophage amastigotes is clearly better positioned than the others as an interesting molecular template for further development of new anti-leishmanial agents

Exploring the views of infection consultants in England on a novel delinked funding model for antimicrobials: the SMASH study

OBJECTIVES: A novel ‘subscription-type’ funding model was launched in England in July 2022 for ceftazidime/avibactam and cefiderocol. We explored the views of infection consultants on important aspects of the delinked antimicrobial funding model. METHODS: An online survey was sent to all infection consultants in NHS acute hospitals in England. RESULTS: The response rate was 31.2% (235/753). Most consultants agreed the model is a welcome development (69.8%, 164/235), will improve treatment of drug-resistant infections (68.5%, 161/235) and will stimulate research and development of new antimicrobials (57.9%, 136/235). Consultants disagreed that the model would lead to reduced carbapenem use and reported increased use of cefiderocol post-implementation. The presence of an antimicrobial pharmacy team, requirement for preauthorization by infection specialists, antimicrobial stewardship ward rounds and education of infection specialists were considered the most effective antimicrobial stewardship interventions. Under the new model, 42.1% (99/235) of consultants would use these antimicrobials empirically, if risk factors for antimicrobial resistance were present (previous infection, colonization, treatment failure with carbapenems, ward outbreak, recent admission to a high-prevalence setting). Significantly higher insurance and diversity values were given to model antimicrobials compared with established treatments for carbapenem-resistant infections, while meropenem recorded the highest enablement value. Use of both ‘subscription-type’ model drugs for a wide range of infection sites was reported. Respondents prioritized ceftazidime/avibactam for infections by bacteria producing OXA-48 and KPC and cefiderocol for those producing MBLs and infections with Stenotrophomonas maltophilia, Acinetobacter spp. and Burkholderia cepacia. CONCLUSIONS: The ‘subscription-type’ model was viewed favourably by infection consultants in England