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Refereed/Peer-reviewed Pathogenic variants in DNMT3A are most commonly associated with Tatton-Brown-Rahman Syndrome (TBRS), but includes other phenotypes such as Heyn-Sproul-Jackson syndrome and acute myeloid leukemia (AML). We describe a patient presenting to the neuromuscular clinic with a de novo missense variant in DNMT3A where the striking clinical feature is that of a congenital myopathy with associated episodes of rhabdomyolysis, severe myalgias and chest pain along with phenotypic features associated with TBRS. Muscle biopsy showed minor myopathic features and cardiac investigations revealed mildly impaired bi-ventricular systolic function. We confirmed the DNA methylation profile matched haplo-insufficient TBRS cases, consistent with a loss of methyltransferase activity. Our report emphasizes the phenotypic overlap of patients with syndromic disorders presenting to neuromuscular clinics and limitations of gene panels in establishing a molecular diagnosis.

Biallelic pathogenic variants in theANO10gene cause spinocerebellar ataxia recessive type 10. We report two patients, both compound heterozygous forANO10variants, including two novel variants. Both patients had onset of cerebellar ataxia in adulthood with slow progression and presented corticospinal tract signs, eye movement abnormalities and cognitive executive impairment. One of them had temporal lobe epilepsy and she also carried a heterozygous variant inCACNB4, a potential risk gene for epilepsy. Both patients had pronounced cerebellar atrophy on cerebral magnetic resonance imaging (MRI) and reduced metabolic activity in cerebellum as well as in the frontal lobes on 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography ((18F)FDG PET) scans. We provide comprehensive clinical, radiological and genetic data on two patients carrying likely pathogenicANO10gene variants. Furthermore, we provide evidence for a cerebellar as well as a frontal involvement on brain (18F)FDG PET scans which has not previously been reported.

Even subtle forms of hemispatial neglect after stroke negatively affect the performance of daily life tasks, increase the risk of injury, and are associated with poor rehabilitation outcomes. Conventional paper-and-pencil tests, however, often underestimate the symptoms. We aimed to identify relevant neglect-specific measures and clinical decision rules based on machine learning techniques on behavioral data generated in a new Virtual Reality (VR) application, the immersive virtual road-crossing task. In total, 59 participants were included in our study: Two right-hemispheric stroke groups with left neglect (n = 20) or no neglect (n = 19), classified based on conventional tests and medical diagnosis, and healthy controls (n = 20). A neuropsychological test battery and the VR task were administered to all participants. We applied decision trees and random forest models to predict the respective groups based on the results of the VR task. Our feature selection procedure yielded six features as suitable predictors, most of which involved lateral time-related measures, particularly reaction times, and head movements. Our model achieved a high training accuracy of 96.6% and, after cross-validation, an accuracy of 76.8%. These results confirm previous reports that temporal behavioral patterns are key to detecting subtle neglect in patients with chronic stroke. Our results indicate that VR combined with machine learning has the potential to achieve higher test accuracies while being highly applicable to clinical practice.

Exercise; Older adults; Sleep quality Ejercicio; Adultos mayores; Calidad de sueño Exercici; Adults grans; Qualitat del son Background: Given the beneficial effects of exercise in different populations and the close relationship between healthy ageing and sleep quality, our objective was to determine if physical exercise delivered through a structured program improves sleep quality in older adults. Methods: Embase, PubMed/MEDLINE, Web of Science, and Cochrane Register of Clinical Trials (CENTRAL) were searched to 15 January 2023. Studies that applied physical exercise programs in older adults were reviewed. Two independent reviewers analysed the studies, extracted the data, and assessed the quality of evidence. Results: Of the 2599 reports returned by the initial search, 13 articles reporting on 2612 patients were included in the data synthesis. The articles used interventions based on yoga (n = 5), multicomponent exercise (n = 3), walking (n = 2), cycling (n = 1), pilates (n = 1), elastic bands (n = 1), and healthy beat acupunch (n = 1). In the intervention group, we found significant improvement in Pittsburgh sleep quality index of −2.49 points (95% CI −3.84 to −1.14) in comparison to the control group (p = 0.0003) and sleep efficiency measured with objective instruments (MD 1.18%, 95% CI 0.86 to 1.50%, p < 0.0001). Conclusion: Our results found that physical exercise programs in older adults improve sleep quality and efficiency measured with objective instruments.

BACKGROUND: For palliative drainage of inoperable perihilar cholangiocarcinoma (pCCA) uncovered metal stents are preferred over plastic stents. However, there is a lack of data on re-interventions at the long-term. The aim is to evaluate the potential difference in the number of re-interventions in patients surviving at least 6 months.METHODS: Retrospective study including patients with pCCA who underwent plastic stent placement(s) or had metal stent(s) in situ for at least 6 months. The primary outcome was the number of re-interventions per patient-year. A propensity score matching (1:1) analysis was performed using age, Bismuth classification, reason for inoperability, pathological confirmation, systemic therapy and initial approach (endoscopic vs percutaneous).RESULTS: Patients in the metal stent group (n = 87) underwent fewer re-interventions compared with the plastic stent group (n = 40) (3.0 vs. 4.7 per patient-year; IRR, 0.64; 95% CI, 0.47 to 0.88). When only non-elective re-interventions were included, there was no significant difference (2.1 vs. 2.7; IRR, 0.76; 95% CI, 0.55 to 1.08). Results were similar in the propensity score-matched dataset.CONCLUSIONS: This study shows that, also in patients with inoperable pCCA who survive at least 6 months, placement of metal stent(s) leads to fewer re-interventions in comparison with plastic stents.

Purpose: To investigate the agreement between an online nurse-assisted eye-screening tool and reference tests in older adults receiving home healthcare and to collect user experiences. Methods: Older adults (65+) receiving home healthcare were included. Home healthcare nurses assisted in administering the eye-screening tool at participants' homes. Approximately 2 weeks later, a researcher administered reference tests at participants' homes. Experiences from participants and home healthcare nurses were collected. Agreement in outcomes (distance and near visual acuity, with the latter being measured using two different optotypes, and macular problems) between the eye-screening tool and reference clinical testing was compared. A difference of less than ±0.15 logMAR was considered acceptable. Results: A total of 40 participants were included. Here, we describe the results for the right eye; results for the left eye were similar. The mean difference between the eye-screening tool and reference tests for distance visual acuity was 0.02 logMAR. The mean difference between the eye-screening tool and reference tests using two different optotypes for near visual acuity was 0.06 and 0.03 logMAR, respectively. The majority of the individual data points were within the ±0.15 logMAR threshold (75%, 51% and 58%, respectively). The agreement between tests for macular problems was 75%. Participants and home healthcare nurses were generally satisfied with the eye-screening tool, although remarks for further improvements were made. Conclusions: The eye-screening tool is promising for nurse-assisted eye screening in older adults receiving home healthcare, with the mostly satisfactory agreement. After implementing the eye-screening tool in practice, cost-effectiveness needs to be investigated.

The study examines illegal and immoral contracts and the legal effects of same. The legal order imposes a multitude of restrictions on the freedom of contract, which is afforded relevance by means of the protection of property embedded in Section 15 of the Constitution of Finland. One of the most salient prerequisites for the binding nature of a contract is its non-contravention of the law or good morals. The study systematises the prohibitory provisions pertaining to legal acts. The method of legal dogmatics is employed to explore the criteria for identifying, whether a legal act contravenes the law or good morals, and a position is taken concerning the types of factors that should be considered in the interpretation of whether a legal act contravenes any given prohibition. The study entails an extensive review of the Finnish case law and legal literature involving legal acts contravening the law and good morals. The study also entails an extensive perusal of the case law of the supreme courts of other Nordic countries, as well as the opinions presented in the legal literature of same. The aspects that are evaluated in relation to legal acts contravening the law and good morals include the manner in which fundamental rights and the interpretational practice of the Constitutional Law Committee impact the determination of legal acts contravening the law and good morals. Particular emphasis is placed on assessing the relationship between the protection of property under Section 15 of the Constitution of Finland and the legal protection afforded under Section 21 thereof, and the generic prohibition against acts contravening good morals. The study suggests that fundamental rights may have an expansionary impact on the freedom of contract. The interpretation of an act contravening common good morals should especially consider the individual’s right to self-determination and the right inherent therein to undertake a variety of binding legal acts. It has been considered that the customary legal consequence of legal acts contravening the law and good morals is invalidity. The premise that has been adopted is that contracts contravening the law or good morals cannot be directed to be carried out, and claims based on same are also otherwise not afforded protection of legitimate expectations. Legal acts contravening the law and good morals have been subject to the so-called principle of unenforceability, which entails that a receivable based on such legal acts cannot be collected through judicial means, and payments transmitted based on such legal acts cannot be recovered, even in cases where the other party has defaulted on their contractual obligation. The study highlights that the stance adopted in legal literature towards legal acts contravening the law and good morals has been inconsistent. When determining the legal effects of contracts contravening the law and good morals, the rulings issued have been somewhat diverse. Particularly the assessment of the relationship of the non-interference principle to the obligation to reimburse payments and restitution ensuing from invalidity has varied across rulings. The study assesses the relationship between the non-interference principle and the fundamental underlying principles of the legal order and the law of obligations. One of these is the prohibition against unilateral gains and the restitution related to same. The non-interference principle is evaluated in relation to the prohibition against financial gain well-established within the sphere of criminal law and the restrictions pertaining to criminal sanctions imposed by the Constitutional Law Committee. The study suggests that in assessing whether a legal act is in contravention of the law and the ensuing invalidity, attention should be paid to the purpose of the prohibitory provision, the efficacy of the prohibition, third-party protection and good faith protection. It is, furthermore, suggested that through waiving the application of the noninterference principle, it is feasible to attain more equitable resolutions from the perspective of the legal order as a whole, in individual cases. Reconciling the requirement of compliance with the law and good morals, based on public interest and the objective perception of morality, and the non-interference principle with the legal order comprised of the legal norms in force, is a difficult task. Väitöskirjassa tarkastellaan lain ja hyvän tavan vastaisia oikeustoimia ja niiden oikeusvaikutuksia. Perustuslain 15 §:n omaisuudensuojan kautta merkitystä saavaa sopimusvapautta rajoitetaan oikeusjärjestyksessä monin eri tavoin. Yksi keskeinen sopimuksen sitovuuden edellytys on, että sopimus ei ole lain tai hyvän tavan vastainen. Lain ja hyvän tavan vastaisten oikeustoimien osalta arvioidaan sitä, millä tavalla perusoikeudet ja perustuslakivaliokunnan tulkintakäytäntö vaikuttavat lain ja hyvän tavan vastaisten oikeustoimien oikeusvaikutusten määräämiseen. Erityisesti arvioidaan PL 15 §:n omaisuudensuojan ja PL 21 §:n oikeusturvan suhdetta yleiseen hyvän tavan vastaisuuden kieltoon. Tutkimuksessa esitetään, että perusoikeuksilla voi olla sopimusvapautta lisäävä vaikutus. Erityisesti yleisen hyvän tavan mukaisuuden vaatimuksen tulkinnassa tulee huomioida yksilöiden itsemääräämisoikeus ja siihen sisältyvä oikeus tehdä erilaisia velvoittavia oikeustoimia. Lain ja hyvän tavan vastaisten oikeustoimien yleisenä oikeusseuraamuksena on pidetty pätemättömyyttä. Lähtökohtana on pidetty sitä, ettei lain tai hyvän tavan vastaisia sopimuksia voida määrätä täytettäviksi eivätkä niihin perustuvat vaatimukset muutoinkaan saa oikeussuojaa. Lain ja hyvän tavan vastaisiin oikeustoimiin on sovellettuna ns. puuttumattomuusperiaatetta, joka tarkoittaa, ettei tällaiseen oikeustoimeen perustuvaa saatava voida periä oikeusteitse eikä tällaisen oikeustoimen perusteella tehtyjä suorituksia ole mahdollista saada takaisin edes niissä tapauksissa, joissa toinen osapuoli on jättänyt sopimuksen mukaisen suoritusvelvollisuutensa täyttämättä. Tutkimuksessa tuodaan esille, että oikeuskäytännössä suhtautuminen lain ja hyvän tavan vastaisiin oikeustoimiin on ollut epäyhtenäistä. Lain ja hyvän tavan vastaisten sopimusten oikeusvaikutusten määräämisessä on annettu osin eri suuntaisia ratkaisuja. Erityisesti puuttumattomuusperiaatteen suhdetta pätemättömyydestä seuraavaan suoritusten palautusvelvollisuuteen ja perusteettoman edun palautukseen on arvioitu ratkaisuissa eri tavoin. Tutkimuksessa esitetään, että oikeustoimen lain ja hyvän tavan vastaisuuden tunnistamiseksi on kehitettävä systemaattisempi lähestymistapa. Lisäksi esitetään, että puuttumattomuusperiaatteen soveltamisesta luopumalla voidaan saavuttaa yksittäisissä tapauksissa oikeusjärjestyksen kokonaisuuden näkökulmasta oikeudenmukaisempia ratkaisuja. Yleiseen etuun ja objektiiviseen moraalikäsitykseen perustuva yleinen lain ja hyvän tavan mukaisuuden vaatimus ja puuttumattomuusperiaate ovat vaikeasti yhteensovitettavissa voimassa olevien oikeusnormien muodostaman oikeusjärjestyksen kokonaisuuden kanssa.

Background Over the past decades, the therapeutic landscape has markedly changed for patients with metastatic solid cancer, yet few studies have evaluated its effect on population-based survival. The objective of this study was to evaluate the change in survival of patients with de novo metastatic solid cancers during the last 30 years. Methods For this retrospective study, data from almost 2 million patients diagnosed with a solid cancer between January 1, 1989, and December 31, 2018, were obtained from the Netherlands Cancer Registry, with follow-up until January 31, 2021. We classified patients as with or without de novo metastatic disease (M1 or M0, respectively) at diagnosis and determined the proportion with M1 disease over time. Changes in age-standardized net survival were calculated as the difference in the 1- and 5-year survival rates of patients diagnosed in 1989-1993 and 2014-2018. Results Different cancers showed divergent trends in the proportion of M1 disease and increases in net survival for M1 disease (approximately 0-50 percentage points at both 1 and 5 years). Patients with gastrointestinal stromal tumors saw the largest increases in 5-year survival, but we also observed substantial 5-year survival increases for patients with neuroendocrine tumors, melanoma, prostate cancer, and breast cancer. Conclusion Over 30 years, the survival of patients with de novo M1 disease modestly and unevenly increased among cancers. Metastatic cancer still remains a very lethal disease. Next to better treatment options, we call for better preventive measures and early detection to reduce the incidence of metastatic disease.

Abstract: This study introduces a 3-week group program designed for patients with neurocognitive post-COVID-19 syndrome (PCS). The program represents a combination of evidence-based components of neurorehabilitation and cognitive behavioral therapy (CBT). Following a detailed assessment, we develop a personalized bio-psycho-social model that integrates perceived complaints and identifies modifiable and influencing factors. We employed physiotherapeutic, cognitive, and communicative training methods to improve patients’ awareness of energy limits and implement compensatory strategies, including pacing and mindfulness techniques. N = 33 patients completed the program between June 2021 and November 2022. A pre-post comparison of questionnaire-based self-assessments revealed significant positive effects on mood, self-efficacy, and participation but not on fatigue symptoms. The study provides recommendations for the neuropsychological treatment of patients with PCS.

Milk is a very complex nutrient and differs significantly between species. Monotreme and Marsupial milk contains only trace amounts of lactose, whereas in Eutherian species, lactose is the predominant saccharide. Within the Eutheria, the composition varies from 8.5% in Indian rhinoceros to 63.8% in Grey seal in concentration; from 0.3% in Indian rhinoceros to 9.3% in elephants in total fat; from 1.2% in Indian rhinoceros to 12.8% in Fin whale in total protein; and finally from 0.8% in Great panda to 6.5% in Indian rhinoceros in lactose. Milk components change during lactation and, especially in Marsupials, this should be considered in artificial feeding. Other factors to be taken into account are the amino acid panel, whey and casein fractions, iron and immunological components. In wildlife nursing, we often come across orphaned neonates that require artificial feeding. However, there are no specific formulas for each wildlife baby. The aim of this review is to compare which artificial milk replacer is best suited for selected species of wildlife neonates., Mlijeko je vrlo kompleksna hrana i znatno se razlikuje od vrste do vrste. Mlijeko jednootvora i tobolčara laktozu sadrži samo u tragovima, dok je u viših sisavaca ona prevladavajući ugljikohidrat. U viših sisavcima, koncentracija laktoze se kreće od: 8,5 % u indijskih nosoroga do 63,8 % u sivih tuljana. Ukupne masnoće kreću se od: 0,3 % u indijskih nosoroga do 9,3 % u slonova. Ukupne bjelančevine od 1,2 % u indijskih nosoroga do 12,8 % u kitova perajara i na kraju laktoza od 0,8 % u velikih panda do 6,5 % u indijskih nosoroga. Sastav mlijeka se tijekom laktacije mijenja, na što je posebno potrebno paziti prilikom hranjena tobolčara umjetnim mlijekom. Drugi čimbenici na koje je potrebno paziti su: panel aminokiselina, frakcije sirutke i kazeina, željezo i imunološke komponente. Kod skrbi za divlje životinje često pronalazimo novorođenu siročad koju je potrebno hraniti umjetnim mlijekom. Međutim, ne postoje posebne formule za svako mladunčedivlje životinje. Cilj je ovog preglednog rada bio usporediti koja je umjetna zamjena za mlijeko najprikladnija za novorođenčad divljih životinja određene vrste.

Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix®.

The longevity of patients with chronic lymphocytic leukemia (CLL) has improved progressively over the past decades, making it essential to understand long-term health outcomes, such as second primary malignancies (SPMs). Therefore, this nationwide, population-based study assessed the risk of SPM development in CLL patients diagnosed during 1989-2019 in the Netherlands compared to the expected number of malignancies in an age-, sex-, and period-matched group from the general Dutch population. In 24,815 CLL patients followed for 162,698.49 person-years, 4369 SPMs were diagnosed with a standardized incidence ratio (SIR) of 1.63 (95% confidence interval [CI] 1.59–1.68). This elevated risk was observed for solid (SIR, 1.67; 95% CI, 1.65–1.75) and hematological SPMs (SIR 1.42; 95% CI, 1.24–1.62). The highest risk for SPMs was noted beyond five years post-diagnosis (SIR, 1.70; 95% CI, 1.62–1.77), for male individuals (SIR, 1.70; 95% CI, 1.64–1.77), and patients aged 18–69 years (SIR, 1.92; 95% CI, 1.79–2.05). The risk of SPMs was higher in CLL patients who received anti-neoplastic therapy (SIR, 2.12; 95% CI, 1.96–2.28), as compared with those who did not (SIR, 1.58; 95% CI, 1.53–1.63). Routine surveillance activities and tailored interventions to counteract the increased morbidity and excess mortality associated with SPMs are essential for improving long-term outcomes in CLL patients.

Purpose: The kidneys serve as the excretory organ of the body. The assessment of serum creatinine, urea, and electrolytes (Na+, K+, HCO3-, Cl-) are crucial and sensitive biochemical markers that are usually involved in the diagnosis of renal impairments (Agbasi et al. 2010; Tietz, 2008; Yakubu et al. 2003). Methodology: Thirty-six animals were grouped into 6, with 6 rats in each group. The animals were housed at room temperature in metal cages. Animals in each group had access to clean water and commercial standard rodent pellets. Group 1 (control group) received distilled water, Groups 2-6 were treated orally with low, middle, and high doses of ethanolic extract of Justicia secunda leaves daily for 42 days. Findings: A significant increase in the level of urea concentration was observed compared to the control. From the present study, Na+, K+, Cl-, and HCO3 increased significantly in the moderate and high dose groups. Unique contribution to theory, policy and practice: In conclusion, this study indicates that ethanolic extract of Justicia secunda increased the serum level of urea, creatinine, and electrolytes.

Contains fulltext : 287484.pdf (Publisher’s version ) (Open Access) BACKGROUND: Iron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear. METHODS: We conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson's disease who had never received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral deferiprone at a dose of 15 mg per kilogram of body weight twice daily or matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed necessary for symptom control. The primary outcome was the change in the total score on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores indicating more severe impairment) at 36 weeks. Secondary and exploratory clinical outcomes at up to 40 weeks included measures of motor and nonmotor disability. Brain iron content measured with the use of magnetic resonance imaging was also an exploratory outcome. RESULTS: A total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P

Durchflusszytometrische Ploidiebestimmungen von untersuchten Senecio-Arten lassen auf Tetraploidie schließen. S. aquaticus aus dem Alpenvorland wies geringere relative DNA-Gehalte als Pflanzen aus anderen Gebieten auf. Messungen von Scrophularia umbrosa s. l. bestätigen und ergänzen die bisher bekannte Verbreitung von S. neesii und S. umbrosa s. str. in Deutschland. Messungen von Aira ergaben keinen Hinweis auf ein Vorkommen von A. multiculmis an den untersuchten Standorten.

Participation in various types of gambling is associated with age and gender. Younger men tend to be drawn toward online gambling whereas women and older individuals tend to engage more in land-based gambling such as electronic gaming machines (EGMs). The present study examined how annual trends in theoretical loss, a robust measure of risk propensity/gambling intensity, varied according to age groups and gender among an EGM-population in Norway (N = 195,318, 26.5% women, age range 18 to 103 years [M = 40.13, SD = 16.29]). Quantile regression on the 25th percentile, median, and 90th percentile theoretical loss showed that higher theoretical loss at these quantiles were associated with older age. At the 90th percentile: Individuals aged 60–69 years had highest theoretical loss at 15,343 NOK (1,784 USD). Compared to men, women had higher 90th percentile theoretical loss (1,658 NOK≈193 USD). Interaction analyses showed that the positive association between age and theoretical loss was stronger for men compared to women. Gambling expenditure is positively associated with disordered gambling and the findings suggests that older individuals and women represent more vulnerable groups among the EGM population. publishedVersion

A new genus and species, Venturioscypha nigropila, is proposed for a minute inoperculate discomycete with long, cylindrical, partly flexuous, dark blackish-brown, smooth, finally thick-walled hairs. It has been collected repeatedly in Europe on dead, corticated branches of Pinus spp. attached to living or recently dead trees. At first glance the species resembles members of Pirottaea (Pyrenopezizaceae), but the relationship is shown by molecular phylogenetics to be close to Hyphodiscus, Hyphopeziza, Fuscolachnum, and Venturiocistella (Hyphodiscaceae). These genera differ in having hairs with more or less conspicuous warts, in Hyphopeziza also with glassy solidifications, and Venturiocistella in having in addition long, stiff, thick-walled, apically acute, dark brown hairs, which are warted in their lower part. The hair wall of Venturioscypha appears superficially smooth, but the surface is inconspicuously pitted as viewed under light microscopy. Venturioscypha is unique in Hyphodiscaceae by its peculiar hairs, inamyloid asci with a thin apical wall that ruptures irregularly by a terminal split at spore discharge, spores with a delicate sheath, and apothecial proliferation.

El proyecto de innovación que se presenta en este trabajo tiene como finalidad reforzar y poner en valor la formación inicial online de los docentes (hombres y mujeres) como agentes impulsores del cambio social. En este sentido, se plantean dos objetivos principales, que se concretan, a su vez, en objetivos secundarios, así como una serie de tareas específicas determinantes para la formación inicial del docente en entornos online. El primero de ellos aborda la necesidad de formar profesionales con un claro perfil crítico, reflexivo y consciente de la responsabilidad social y moral que supone la profesión docente. El segundo, por su parte, tiene como meta el refuerzo y la optimización del periodo de prácticas externas por ser un aspecto determinante en la formación inicial docente. Este proyecto de innovación comenzó en enero de 2021 y tuvo una duración de un año. En él participó un equipo multidisciplinar de docentes de las distintas áreas de conocimiento (pedagogía, psicología, geografía e historia, lingüística y literatura) de la Facultad de Ciencias de la Salud y la Educación de la Universidad a Distancia de Madrid, UDIMA. Sus integrantes unieron sinergias para el trabajo colaborativo a través de la metodología denominada «investigación-acción», de carácter eminentemente práctico y enfocada al aula virtual. Los primeros resultados que arroja el presente proyecto apuntan a la necesidad de un cambio metodológico y de recursos didácticos en la formación inicial docente online.

In the context of the digital transformation, the targeted implementation of AI-based or AI-supported technologies in "teaching & learning" as well as "administration & service" holds considerable potential for organizational change and quality enhancement for higher education institutions. The use of AI in higher education teaching and services lags behind the level in research. Therefore, holistic solutions must be planned and implemented in unity of teaching and research for the AI-based support of the stakeholders’ inclusive administration, the further development or the establishment of new digital study programs and offers as well as the prospective qualification of university staff in the field of AI. The solutions must be analyzed, systematized, and structured to generate a conceptual approach via an integrated architecture with adaptive services. This paper is an evolution of the concept presented at the Learning Ideas Conference 2022 and includes, in addition to explanations of the current state of the arts, the presentation of a systems-oriented approach for AI in higher education as well as the conception of the student lifecycle management at the author’s university. The paper ends with the presentation of a concept regarding a decision support system for individualized studying.

The mergers of supermassive black hole binaries (SMBHBs) can serve as standard sirens: the gravitational wave (GW) analog of standard candles. The upcoming space-borne GW detectors will be able to discover such systems and estimate their luminosity distances precisely. Unfortunately, weak gravitational lensing can induce significant errors in the measured distance of these standard sirens at high redshift, severely limiting their usefulness as precise distance probes. The uncertainty due to weak lensing can be reduced if the lensing magnification of the siren can be estimated independently, a procedure called 'delensing'. With the help of up-to-date numerical simulations, here we investigate how much the weak-lensing errors can be reduced using convergence maps reconstructed from shear measurements. We also evaluate the impact of delensing on cosmological parameter estimation with bright standard sirens. We find that the weak-lensing errors for sirens at $z_s = 2.9$ can be reduced by about a factor of two on average, but to achieve this would require expensive ultra-deep field observations for every siren. Such an approach is likely to be practical in only limited cases, and the reduction in the weak-lensing error is therefore likely to be insufficient to significantly improve the cosmological parameter estimation. We conclude that performing delensing corrections is unlikely to be worthwhile, in contrast to the more positive expectations presented in previous studies. For delensing to become more practicable and useful in the future will require significant improvements in the resolution/depth of weak-lensing surveys and/or the methods to reconstruct convergence maps from these surveys., 20 pages, 22 figures, to be published in MNRAS

Reconstructing the history of polar temperature from ice core water isotope (δ18O) calibration has remained a challenge in paleoclimate research, because of our incomplete understanding of various temperature–δ18O relationships. This paper resolves this classical problem in a new framework called the unified slope equations (USE), which illustrates the general relations among spatial and temporal δ18O–surface temperature slopes. The USE is applied to the Antarctica temperature change during the last deglaciation in model simulations and observations. It is shown that the comparable Antarctica-mean spatial slope with deglacial temporal slope in δ18O–surface temperature reconstruction is caused, accidentally, by the compensation responses between the δ18O–inversion layer temperature relation and the inversion layer temperature itself. Furthermore, in light of the USE, we propose that the present seasonal slope of δ18O–inversion layer temperature is an optimal paleothermometer that is more accurate and robust than the spatial slope. This optimal slope suggests the possibility of reconstructing past Antarctic temperature changes using present and future instrumental observations. Significance Statement This paper develops a new framework called the unified slope equations (USE) to provide, for the first time, a general relation among various spatial and temporal water isotope–temperature slopes. The application of the USE to Antarctic deglacial temperature change shows that the optimal paleothermometer is the seasonal slope of the inversion layer temperature.

This study examined the impact of fiscal federalism on economic development in Nigeria over the period 1981 to 2020 using annual time series. Both revenue and expenditure decentralization were used as measures of fiscal federalism. Analytically, the study employed the autoregressive distributed lag approach. The result reveals that in the long run, revenue and expenditure decentralization have a positive and significant impact on economic development in Nigeria, and many scholars have validated this finding. This finding shows that true fiscal federalism is better captured by both subnational revenue and expenditure decentralization. Given the finding, the study suggests that more fiscal power should be devolved to state and local governments in Nigeria through appropriate legislation.

Abstract: In this research, we propose that belief in a just world (BJW) can be divided into two distinct beliefs: one addressing the notion that efforts are rewarded, that is, effort-based BJW, and another maintaining that the valence associated with moral character leads to particular consequences, that is, valence-based BJW (e.g., good people are rewarded and bad people are punished). We used culturally relevant proverbs to design measures in German and Chinese. Samples of college students and working adults from both countries were collected to assess the reliability, factor structure, validity, and the nomological consistency of the newly developed measures. Both measures demonstrated strong evidence of the existence of and distinction between effort- and valence-based BJW, and they displayed unique patterns in predicting different variables beyond the effect of personal BJW and BJW for others, which may elucidate the precise justice beliefs related to different phenomena.

Malonyl-CoA is a central precursor for biosynthesis of a wide range of complex secondary metabolites. The development of platform strains with increased malonyl-CoA supply can contribute to the efficient production of secondary metabolites, especially if such strains exhibit high tolerance towards these chemicals. In this study, Pseudomonas taiwanensis VLB120 was engineered for increased malonyl-CoA availability to produce bacterial and plant-derived polyketides. A multi-target metabolic engineering strategy focusing on decreasing the malonyl-CoA drain and increasing malonyl-CoA precursor availability, led to an increased production of various malonyl-CoA-derived products, including pinosylvin, resveratrol and flaviolin. The production of flaviolin, a molecule deriving from five malonyl-CoA molecules, was doubled compared to the parental strain by this malonyl-CoA increasing strategy. Additionally, the engineered platform strain enabled production of up to 84 mg L−1 resveratrol from supplemented p-coumarate. One key finding of this study was that acetyl-CoA carboxylase overexpression majorly contributed to an increased malonyl-CoA availability for polyketide production in dependence on the used strain-background and whether downstream fatty acid synthesis was impaired, reflecting its complexity in metabolism. Hence, malonyl-CoA availability is primarily determined by competition of the production pathway with downstream fatty acid synthesis, while supply reactions are of secondary importance for compounds that derive directly from malonyl-CoA in Pseudomonas.

Using data on the registration of clinical trials and the disclosure of trial results, we examine how firms respond to peer disclosures. We find that firms are less likely to disclose their own trial results if the results of a larger number of closely related trials are disclosed by their peers. This relation is stronger if the firms face higher competition (as measured by the number of competing trials). It is weaker if the firms are further along in their research than the peers (as measured by the trials’ phase) and if the peers’ disclosures convey more negative news (as measured by the firms’ stock price reaction). We also find that firms are more likely to abandon ongoing trials if a larger number of peers disclose the results of closely related trials. Additional tests suggest that this real effects channel does not drive the impact on the firms’ disclosure decisions. Data Availability: Data are available from the public sources cited in the text. JEL Classifications: M4.

Type 2 diabetes (T2D) is a growing problem in children. Children with NAFLD are at potentially high risk for developing T2D; however, the incidence of T2D in this population is unknown. This study aimed to determine the incidence of T2D in children with NAFLD and identify associated risk factors.Children with NAFLD enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network were followed longitudinally. Incidence of T2D was determined by using clinical history and fasting laboratory values. Cumulative incidence curves were developed for time to T2D. A Cox regression multivariable model was constructed using best subsets Akaike's Information Criteria selection.This study included 892 children with NAFLD and with a mean age of 12.8 years (2.7) followed for 3.8 years (2.3) with a total 3234 person-years at risk. The incidence rate of T2D was 3000 new cases per 100,000 person-years at risk. At baseline, 63 children had T2D, and during follow-up, an additional 97 children developed incident T2D, resulting in a period prevalence of 16.8%. Incident T2D was significantly higher in females versus males (hazard ratio [HR], 1.8 [1.0-2.8]), associated with BMI z-score (HR, 1.8 [1.0-3.0]), and more severe liver histology including steatosis grade (HR, 1.3 [1.0-1.7]), and fibrosis stage (HR, 1.3 [1.0-1.5]).Children with NAFLD are at high risk for existing and incident T2D. In addition to known risk factors for T2D (female and BMI z-score), severity of liver histology at the time of NAFLD diagnosis was independently associated with T2D development. Targeted strategies to prevent T2D in children with NAFLD are needed.

This research is a literature study that aims to dig up information related to creativity and innovation in teaching philosophy. Philosophy is a scientific discipline that requires critical and creative thinking, but teaching philosophy often feels monotonous and boring for some students. Therefore, this research wants to find various creative and innovative strategies that can be applied in teaching philosophy to make it more attractive and motivating for students. The method used in this research is literature study by collecting and analyzing various journal articles, books, and information sources related to creativity and innovation in teaching philosophy. The results of this study are expected to contribute to the development of more creative and innovative philosophy teaching strategies and to motivate students to learn philosophy better.

Associating multiple sensory cues with objects and experience is a fundamental brain process that improves object recognition and memory performance. However, neural mechanisms that bind sensory features during learning and augment memory expression are unknown. Here we demonstrate multisensory appetitive and aversive memory in Drosophila. Combining colours and odours improved memory performance, even when each sensory modality was tested alone. Temporal control of neuronal function revealed visually selective mushroom body Kenyon cells (KCs) to be required for enhancement of both visual and olfactory memory after multisensory training. Voltage imaging in head-fixed flies showed that multisensory learning binds activity between streams of modality-specific KCs so that unimodal sensory input generates a multimodal neuronal response. Binding occurs between regions of the olfactory and visual KC axons, which receive valence-relevant dopaminergic reinforcement, and is propagated downstream. Dopamine locally releases GABAergic inhibition to permit specific microcircuits within KC-spanning serotonergic neurons to function as an excitatory bridge between the previously ‘modality-selective’ KC streams. Cross-modal binding thereby expands the KCs representing the memory engram for each modality into those representing the other. This broadening of the engram improves memory performance after multisensory learning and permits a single sensory feature to retrieve the memory of the multimodal experience.