Modulation of the stretch feedback pathway in the cardiac neuromuscular system of the American lobster, \u3ci\u3eHomarus americanus\u3c/i\u3e

The cardiac ganglion (CG) is a central pattern generator, a neural network that, when activated, produces patterned motor outputs such as breathing and walking. The CG induces the heart contractions of the American lobster, Homarus americanus, making the lobster heart neurogenic. In the American lobster, the CG is made up of nine neurons: four premotor pacemaker neurons that send signals to five motor neurons, causing bursts of action potentials from the motor neurons. These bursts cause cardiac muscle contractions that vary in strength based on the burst duration, frequency, and pattern. The activity of the CG is modulated by feedback pathways and neuromodulators, allowing for flexibility in the CG’s motor output and appropriate responses to changes in the animal’s environment. Two feedback pathways modulate the CG motor output, the excitatory cardiac muscle stretch and inhibitory nitric oxide feedback pathways. Despite our knowledge of the modulation of the CG by feedback pathways and neuromodulators separately, little is known about how neuromodulators influence the sensory feedback response to cardiac muscle stretch. I found one neuromodulator to modulate each phase of the stretch response differently, one neuromodulator to generally not affect the stretch response, and three neuromodulators to suppress the stretch response. These results suggest neuromodulators can act to produce flexibility in a CPG’s motor output, allowing the system to respond appropriately to changes in an organism’s environment, and allow for variation in CPG responses to different stimuli

Randomized controlled trial to evaluate the effects of ethyl-2-cyanoacrylate on pain intensity and quality of life in head and neck cancer patients suffering from cetuximab-induced rhagades during radioimmunotherapy: the support trial

Background: Cetuximab is a chimeric monoclonal antibody against the epidermal growth factor receptor (EGFR). Skin reactions are the most common side effects of cetuximab. Rhagades of the tips of the fingers and toes, the heels and especially the interphalangeal joints are one of the most frightening and painful dermatological side effects that may develop from EGFR-inhibitor therapy. Rhagades are characterized by pain, severe tenderness and poor healing response. They are challenging to treat. Thus, rhagades often poses the most significant threat to the quality of life (QoL) for these patients. Ethyl-2-cyanoacrylate (ECA), an ethyl ester of the 2-cyano-2-propenoic acid, is often used as adhesive in a variety of different work settings in industry, i.e. as a component in nail-care products such as nail glue. In addition, ECA is used for various medical indications, such as for liquid bandages and for suture-less surgery. Wound healing can be accelerated with ECA. The purpose of the SUPPORT trial is to investigate the efficacy of ECA for the treatment of cetuximab-induced rhagades and to assess the clinical usefulness of the SUPO score, a new classification system for rhagades induced by EGFR-inhibitor therapy. Methods/Design: The SUPPORT trial is an open-label, prospective, randomized, national multicenter intervention study to evaluate the effectiveness of ECA versus the standard treatment of each institution on the pain intensity and QoL in patients with locally advanced head and neck cancer suffering from painful cetuximab-induced rhagades during radioimmunotherapy. Primary endpoint is the assessment of the pain intensity 24 hours after application of ECA or the standard treatment quantified by the visual analogue scale (VAS). Secondary endpoints are the evaluation of QoL assessed by the EORTC-QoL-C30 questionnaire and the Dermatological Life Quality Index (DLQI). Discussion: During treatment with EGFR inhibitors it is necessary to recognize and manage side effects promptly to assure better patient QoL. The SUPPORT trial is the first randomized clinical trial evaluating a new treatment option for painful cetuximab-induced rhagades. Furthermore, the new SUPO score will be prospectively assessed in terms of clinical usefulness for classification of EGFR inhibitor-induced rhagades. Trial registration: Current Controlled Trials NCT0169315

Brain metastasis and survival outcomes after first-line therapy in metastatic melanoma: a multicenter DeCOG study on 1704 patients from the prospective skin cancer registry ADOREG

Background Despite the availability of effective systemic therapies, a significant number of advanced melanoma patients develops brain metastases. This study investigated differences in incidence and time to diagnosis of brain metastasis and survival outcomes dependent on the type of first-line therapy.Methods Patients with metastatic, non-resectable melanoma (AJCCv8 stage IIIC–V) without brain metastasis at start of first-line therapy (1L-therapy) were identified from the prospective multicenter real-world skin cancer registry ADOREG. Study endpoints were incidence of brain metastasis, brain metastasis-free survival (BMFS), progression-free survival (PFS), and overall survival (OS).Results Of 1704 patients, 916 were BRAF wild-type (BRAFwt) and 788 were BRAF V600 mutant (BRAFmut). Median follow-up time after start of 1L-therapy was 40.4 months. BRAFwt patients received 1L-therapy with immune checkpoint inhibitors (ICI) against CTLA-4+PD-1 (n=281) or PD-1 (n=544). In BRAFmut patients, 1L-therapy was ICI in 415 patients (CTLA-4+PD-1, n=108; PD-1, n=264), and BRAF+MEK targeted therapy (TT) in 373 patients. After 24 months, 1L-therapy with BRAF+MEK resulted in a higher incidence of brain metastasis compared with PD-1±CTLA-4 (BRAF+MEK, 30.3%; CTLA-4+PD-1, 22.2%; PD-1, 14.0%). In multivariate analysis, BRAFmut patients developed brain metastases earlier on 1L-therapy with BRAF+MEK than with PD-1±CTLA-4 (CTLA-4+PD-1: HR 0.560, 95% CI 0.332 to 0.945, p=0.030; PD-1: HR 0.575, 95% CI 0.372 to 0.888, p=0.013). Type of 1L-therapy, tumor stage, and age were independent prognostic factors for BMFS in BRAFmut patients. In BRAFwt patients, tumor stage was independently associated with longer BMFS; ECOG Performance status (ECOG-PS), lactate dehydrogenase (LDH), and tumor stage with OS. CTLA-4+PD-1 did not result in better BMFS, PFS, or OS than PD-1 in BRAFwt patients. For BRAFmut patients, multivariate Cox regression revealed ECOG-PS, type of 1L-therapy, tumor stage, and LDH as independent prognostic factors for PFS and OS. 1L-therapy with CTLA-4+PD-1 led to longer OS than PD-1 (HR 1.97, 95% CI 1.122 to 3.455, p=0.018) or BRAF+MEK (HR 2.41, 95% CI 1.432 to 4.054, p=0.001), without PD-1 being superior to BRAF+MEK.Conclusions In BRAFmut patients 1L-therapy with PD-1±CTLA-4 ICI resulted in a delayed and less frequent development of brain metastasis compared with BRAF+MEK TT. 1L-therapy with CTLA-4+PD-1 showed superior OS compared with PD-1 and BRAF+MEK. In BRAFwt patients, no differences in brain metastasis and survival outcomes were detected for CTLA-4+PD-1 compared with PD-1

Rising employment, rising inequalitiy: Examining labour market development and policy in the third Merkel Government (2013 to 2017)

The German labour market has developed positively in the third term of the Merkel Government. The stable upward trend of the labour market is largely attributable to an increase in part-time employment, often in the service industry and in the low-wage sector. The increased magnitude of employment in the low-wage sector contributed to the solidifying of inequalities in income levels, despite the steady upward trend of employment in general

Hur lärare anpassar undervisningen för elever med språkstörning i årskursintervallet 1-9 i ämnet matematik.

Vi använde oss av en kvalitativ forskningsansats, och som metod använde vi oss av kvalitativa intervjuer, där vi intervjuade tolv lärare/speciallärare i årskursintervallet 1 - 9. Syftet var att undersöka hur lärare/speciallärare beskriver undervisningens hinder och möjligheter för elever med diagnosen språkstörning, i ämnet matematik, inom årskursintervallet 1 - 9. Ytterligare ett syfte var att se hur lärare anpassar undervisningen  för elever med diagnosen språkstörning och matematiksvårigheter. Som dataanalys använde vi oss av att transkribera intervjuerna, koda och kategorisera nyckelord, för att sedan utkristallisera tre huvudteman, Lärarnas undervisningssituation, Svårigheter i undervisningen och Lärares arbete med anpassningar. När vi analyserade resultatet utgick vi från två teoretiska utgångspunkter, det sociokulturella och det rationella perspektivet. Resultatet visade att de områden lärare/speciallärare pratade mest om var begrepp, tid, tydlighet, brist på arbetsminne relationer och anpassningar. De flesta lärare var eniga om att det krävdes en hel del anpassningar, när man hade elever med språkstörning i klassrummet. Som slutsats vill vi säga att alla pedagoger var överens om, att det fanns en tydlig brist på kunskap om att undervisa elever med språkstörning och att mer kunskap önskades

Postoperative wound infections after a proctectomy Patient

AbstractPoor perineal wound healing and infections after proctectomy surgery cause a significant proportion of physical andpsychological morbidities, such as pain, leakage, and abscesses. In the long run, some of these symptoms will lead toextended periods of hospitalization. These kinds of postoperative complications are also associated with delays in possiblechemotherapy treatment. The aim of this study was to describe patient experiences of perineal wound infections followingproctectomy due to rectal cancer, and the importance of the communication with and the self-care support from the nursefor these patients. Five women and five men (61-87 years, median age 71 years) were included and interviewed. Aqualitative content analysis of the interviews was carried out and the following main categories emerged: ‘‘Managingpostoperative complications,’’ ‘‘Being independent,’’ ‘‘Feeling safe,’’ and ‘‘Accepting the situation.’’ A perineal woundinfection after a proctectomy is devastating for the individual patient. The limitations and changes to the patients’ lives turninto new daily routines, which force them to find new ways to live and to accept the situation. For many of them, theinfections remained for several months and, sometimes, for years. The ability to lead an independent life is drasticallyreduced, but through continuity in care it is possible to create a feeling of safety. Information, communication, and self-caresupport are all important and valuable factors for recovery. Specialized care containing an action plan is therefore needed inclinical practice to reduce the number of perineal wound infections postoperatively and should be initiated when the patientis discharged from the ward and continue until recover

Die Rolle der Sozialpartnerschaft in der digitalen Transformation: Stellungnahme für die Enquêtekommission Digitale Transformation der Arbeitswelt in NRW

Die Fragen der Enquêtekommission beziehen sich auf die Rolle der Sozialpartnerschaft in der digitalen Transformation. Die Sozialpartnerschaft in Deutschland weist eine im internationalen Vergleich besondere Arbeitsteilung zwischen gesetzlicher, tariflicher und betrieblicher Regulierung der Arbeit auf. Sie basiert auf der Selbstorganisation der Gewerkschaften und Arbeitgeberverbände im Rahmen gesetzlicher regulierter Mitbestimmung und ist überwiegend branchenspezifisch organisiert. Die größte Herausforderung für die Sozialpartnerschaft in Deutschland ist die seit mehr als dreißig Jahren sinkende Bindungskraft der Verbände und damit verbundene sinkende Handlungsfähigkeit in der Tarifpolitik, aber auch in der betrieblichen Mitbestimmung. Heute liegt der Organisationsgrad der Arbeitnehmerinnen und Arbeitnehmer bei unter 20 % und der Anteil der Beschäftigten in tarifgebundenen Unternehmen in Deutschland bei knapp 50 %. Weniger als 30 % der Beschäftigten arbeiten in Betrieben, die sowohl einen Betriebsrat als auch einen Tarifvertrag haben. Zudem ist die Handlungsfähigkeit der Sozialpartner in den einzelnen Branchen sehr unterschiedlich ausgeprägt (Hassel/Schroeder 2018). Diese Entwicklung vollzieht sich unabhängig von den Herausforderungen der digitalen Transformation und hat bereits in den 1980er Jahren eingesetzt. Sie ist Resultat einer Vielzahl von Faktoren angefangen bei dem Strukturwandel zur Dienstleistungsökonomie, einer zunehmenden Reorganisation von Unternehmen, dem Effekt der deutschen Wiedervereinigung und der Deregulierung des Arbeitsmarktes. Damit die Sozialpartnerschaft eine produktive und problemlösende Rolle in der digitalen Transformation spielen kann, bedarf es einer grundsätzlichen politischen und gesellschaftlichen Unterstützung der Verbände bei der Ausübung ihrer Aufgaben