Weak differentiability of product measures

In this paper, we study cost functions over a finite collection of random variables. For these types of models, a calculus of differentiation is developed that allows us to obtain a closed-form expression for derivatives where "differentiation" has to be understood in the weak sense. The technique for proving the results is new and establishes an interesting link between functional analysis and gradient estimation. The key contribution of this paper is a product rule of weak differentiation. In addition, a product rule of weak analyticity is presented that allows for Taylor series approximations of finite products measures. In particular, from characteristics of the individual probability measures, a lower bound (i.e., domain of convergence) can be established for the set of parameter values for which the Taylor series converges to the true value. Applications of our theory to the ruin problem from insurance mathematics and to stochastic activity networks arising in project evaluation review techniques are provided. © 2010 INFORMS

Union of the European Phoniatricians' position statement on the exit strategy of phoniatric and laryngological services : staying safe and getting back to normal after the peak of coronavirus disease 2019 (issued on 25th May 2020)

Background The following position statement from the Union of the European Phoniatricians, updated on 25th May 2020 (superseding the previous statement issued on 21st April 2020), contains a series of recommendations for phoniatricians and ENT surgeons who provide and/or run voice, swallowing, speech and language, or paediatric audiology services. Objectives This material specifically aims to inform clinical practices in countries where clinics and operating theatres are reopening for elective work. It endeavours to present a current European view in relation to common procedures, many of which fall under the aegis of aerosol generating procedures. Conclusion As evidence continues to build, some of the recommended practices will undoubtedly evolve, but it is hoped that the updated position statement will offer clinicians precepts on safe clinical practice.Peer reviewe

Agrobacterium tumefaciens-mediated transformation of Cleome gynandra L., a C4 dicotyledon that is closely related to Arabidopsis thaliana

In leaves of most C4 plants, the biochemistry of photosynthesis is partitioned between mesophyll and bundle sheath cells. In addition, their cell biology and development also differs from that in C3 plants. We have a poor understanding of the mechanisms that generate the cell-specific accumulation of proteins used in the C4 pathway, and there are few genes that have been shown to be important for the cell biology and development of C4 leaves. To facilitate functional analysis of C4 photosynthesis, and to enable knowledge from Arabidopsis thaliana to be translated to C4 species, an Agrobacterium tumefaciens-mediated transformation protocol was developed for the C4 species Cleome gynandra. A. tumefaciens, harbouring the binary vector SLJ1006, was used to transfer the uidA gene under the control of the CaMV 35S promoter into C. gynandra. Co-incubation of hypocotyls or cotyledons with SLJ1006 allowed efficient transfer of DNA into C. gynandra, and media that allowed callus production and then shoot regeneration were identified. Stable transformants of C. gynandra with detectable amounts of β-glucuronidase (GUS) were produced at an efficiency of 14%. When driven by the CaMV 35S promoter, GUS was visible in all leaf cells, whereas uidA translationally fused to a CgRbcS gene generated GUS accumulation specifically in bundle sheath cells. This transformation procedure is the first for an NAD-ME type C4 plant and should significantly accelerate the analysis of mechanisms underlying C4 photosynthesis

Strategies to Target Tumor Immunosuppression

The tumor microenvironment is currently in the spotlight of cancer immunology research as a key factor impacting tumor development and progression. While antigen-specific immune responses play a crucial role in tumor rejection, the tumor hampers these immune responses by creating an immunosuppressive microenvironment. Recently, major progress has been achieved in the field of cancer immunotherapy, and several groundbreaking clinical trials demonstrated the potency of such therapeutic interventions in patients. Yet, the responses greatly vary among individuals. This calls for the rational design of more efficacious cancer immunotherapeutic interventions that take into consideration the “immune signature” of the tumor. Multimodality treatment regimens that aim to enhance intratumoral homing and activation of antigen-specific immune effector cells, while simultaneously targeting tumor immunosuppression, are pivotal for potent antitumor immunity

Laryngopharyngealer Reflux: Korrelieren Klinik und oropharyngeale 24h-pH-Metrie?

Hintergrund: Ein extraösophagealer oder auch laryngopharyngealer Reflux (LPR) kann ursächlich für zahlreiche Pathologien sein, mit denen insbesondere Phoniater und HNO-Ärzte tagtäglich konfrontiert werden. Die diagnostische Sicherung des LPR stellt noch immer eine Herausforderung dar, da die zur Verfügung stehenden Messinstrumente meist subjektiv, schlecht reproduzierbar und/oder nicht validiert sind. Dies ist auch therapeutisch relevant, da ein unkritischer oder rein diagnostischer Einsatz von Protonenpumpeninhibitoren aufgrund des Nebenwirkungspotenzial abzulehnen ist.Material und Methoden: Analysiert wurden die Daten von 203 Patienten (mittleres Alter 52,8 ± 15,8, w 61,6%), die zwischen November 2014 und März 2018 in unserer Klinik zur oropharyngealen 24h-pH-Metrie vorgestellt wurden. Ausschlusskriterien waren u.a. eine medikamentöse Refluxtherapie oder andere gesicherte Erkrankungen als Primärursache der Beschwerden. Die Ausprägung der Symptome wurde anhand des "Reflux Symptom Index (RSI)" gemessen und laryngoskopische Auffälligkeiten mittels "Reflux Finding Score (RFS)" klassifiziert. Anschließend erfolgte die oropharyngeale 24h-pH-Metrie (Restech Dx-System). Als Bewertungsmaßstab wurde der "Ryan Score", der sich aus Anzahl und Dauer der Reflux Episoden mit pH 9,41) auf, davon wiederum knapp die Hälfte gravierend ausgeprägt (>80,0). Bezogen auf den RSI zeigte sich keine Korrelation, so hatte von den 147 Patienten mit erhöhtem RSI (>13) nicht einmal die Hälfte einen erhöhten Ryan Score. Auch zum RFS ließ sich kein Bezug herstellen, nur 40% der 90 Patienten mit auffälligem RFS wiesen einen erhöhten Ryan Score auf. Zwischen RSI und RFS untereinander konnte ebenfalls keine Korrelation festgestellt werden.Diskussion: Die diskrepanten Ergebnisse der in dieser Studie angewandten Untersuchungsverfahren werden diskutiert und in den Kontext der aktuellen Literatur gestellt.Fazit: Die fehlende Korrelation zwischen den Angaben der Patienten (RSI) und dem laryngoskopischem Befund (RFS) sowie diesen und den Ergebnissen der oropharyngealen 24h-pH-Metrie zeigt, dass es weiterer Studien bedarf, um ein valides Diagnostikregime für den LPR zu definieren