Electrically evoked compound action potentials are different depending on the site of cochlear stimulation.

One of the many parameters that can affect cochlear implant (CI) users' performance is the site of presentation of electrical stimulation, from the CI, to the auditory nerve. Evoked compound action potential (ECAP) measurements are commonly used to verify nerve function by stimulating one electrode contact in the cochlea and recording the resulting action potentials on the other contacts of the electrode array. The present study aimed to determine if the ECAP amplitude differs between the apical, middle, and basal region of the cochlea, if double peak potentials were more likely in the apex than the basal region of the cochlea, and if there were differences in the ECAP threshold and recovery function across the cochlea. ECAP measurements were performed in the apical, middle, and basal region of the cochlea at fixed sites of stimulation with varying recording electrodes. One hundred and forty one adult subjects with severe to profound sensorineural hearing loss fitted with a Standard or FLEX(SOFT) electrode were included in this study. ECAP responses were captured using MAESTRO System Software (MED-EL). The ECAP amplitude, threshold, and slope were determined using amplitude growth sequences. The 50% recovery rate was assessed using independent single sequences that have two stimulation pulses (a masker and a probe pulse) separated by a variable inter-pulse interval. For all recordings, ECAP peaks were annotated semi-automatically. ECAP amplitudes were greater upon stimulation of the apical region compared to the basal region of the cochlea. ECAP slopes were steeper in the apical region compared to the basal region of the cochlea and ECAP thresholds were lower in the middle region compared to the basal region of the cochlea. The incidence of double peaks was greater upon stimulation of the apical region compared to the basal region of the cochlea. This data indicates that the site and intensity of cochlear stimulation affect ECAP properties

Challenging the heterogeneity of disease presentation in malignant melanoma-impact on patient treatment

There is an increasing global interest to support research areas that can assist in understanding disease and improving patient care. The National Cancer Institute (NIH) has identified precision medicine-based approaches as key research strategies to expedite advances in cancer research. The Cancer Moonshot program ( https://www.cancer.gov/research/key-initiatives/moonshot-cancer-initiative ) is the largest cancer program of all time, and has been launched to accelerate cancer research that aims to increase the availability of therapies to more patients and, ultimately, to eradicate cancer. Mass spectrometry-based proteomics has been extensively used to study the molecular mechanisms of cancer, to define molecular subtypes of tumors, to map cancer-associated protein interaction networks and post-translational modifications, and to aid in the development of new therapeutics and new diagnostic and prognostic tests. To establish the basis for our melanoma studies, we have established the Southern Sweden Malignant Melanoma Biobank. Tissues collected over many years have been accurately characterized with respect to the tumor and patient information. The extreme variability displayed in the protein profiles and the detection of missense mutations has confirmed the complexity and heterogeneity of the disease. It is envisaged that the combined analysis of clinical, histological, and proteomic data will provide patients with a more personalized medical treatment. With respect to disease presentation, targeted treatment and medical mass spectrometry analysis and imaging, this overview report will outline and summarize the current achievements and status within malignant melanoma. We present data generated by our cancer research center in Lund, Sweden, where we have built extensive capabilities in biobanking, proteogenomics, and patient treatments over an extensive time period

Electrically evoked compound action potentials are different depending on the site of cochlear stimulation

One of the many parameters that can affect cochlear implant (CI) users' performance is the site of presentation of electrical stimulation, from the CI, to the auditory nerve. Evoked compound action potential (ECAP) measurements are commonly used to verify nerve function by stimulating one electrode contact in the cochlea and recording the resulting action potentials on the other contacts of the electrode array. The present study aimed to determine if the ECAP amplitude differs between the apical, middle, and basal region of the cochlea, if double peak potentials were more likely in the apex than the basal region of the cochlea, and if there were differences in the ECAP threshold and recovery function across the cochlea. ECAP measurements were performed in the apical, middle, and basal region of the cochlea at fixed sites of stimulation with varying recording electrodes. One hundred and forty one adult subjects with severe to profound sensorineural hearing loss fitted with a Standard or FLEX(SOFT) electrode were included in this study. ECAP responses were captured using MAESTRO System Software (MED-EL). The ECAP amplitude, threshold, and slope were determined using amplitude growth sequences. The 50% recovery rate was assessed using independent single sequences that have two stimulation pulses (a masker and a probe pulse) separated by a variable inter-pulse interval. For all recordings, ECAP peaks were annotated semi-automatically. ECAP amplitudes were greater upon stimulation of the apical region compared to the basal region of the cochlea. ECAP slopes were steeper in the apical region compared to the basal region of the cochlea and ECAP thresholds were lower in the middle region compared to the basal region of the cochlea. The incidence of double peaks was greater upon stimulation of the apical region compared to the basal region of the cochlea. This data indicates that the site and intensity of cochlear stimulation affect ECAP properties

Wind modulation of upwelling at the shelf-break front off Patagonia: Observational evidence

The South-Atlantic Patagonian shelf is the largest chlorophyll-a (Chl-a) hot spot in Southern Ocean color images. While a persistent 1500 km long band of high Chl-a along the shelf-break front (SBF) is indicative of upwelling, the mechanisms that drive it are not entirely known. Along-front wind oscillations can enhance upwelling and provide a nutrient pumping mechanism at shelf-break fronts of western boundary currents. Here we assess wind-induced upwelling at the SBF off Patagonia from daily satellite Chl-a and winds, historical hydrographic observations, cross-shelf Chl-a fluorescence transects from two cruises, and in situ winds and water column structure from a mooring site. Satellite Chl-a composites segregated by along-front wind direction indicate that surface Chl-a is enhanced at the SBF with southerly winds and suppressed with northerly winds. Northerly winds also result in enhanced Chl-a further offshore (∼25–50 km). Synoptic transects as well as mean hydrographic sections segregated by along-front winds show isopycnals tilted upward for southerly winds. Spring observations from the mooring also suggest that southerly winds destratify the water column and northerly winds restratify, in agreement with Ekman transport interacting with the front. Moreover, changes in water column temperature lag along-front wind forcing by 2–4 days. Our results suggest that oscillations in along-front winds, on timescales typical of atmospheric storms (2–10 days), can significantly modulate the upwelling and Chl-a concentrations at the SBF off Patagonia, revealing the importance of wind-induced upwelling for shelf-slope exchange at shelf-break fronts of western boundary currents.Fil: Carranza, Magdalena. University of California at San Diego. Scripps Institution of Oceanography; Estados UnidosFil: Gille, Sarah. University of California at San Diego. Scripps Institution of Oceanography; Estados UnidosFil: Piola, Alberto Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Ministerio de Defensa. Armada Argentina. Servicio de Hidrografía Naval. Departamento Oceanografía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias de la Atmósfera y los Océanos; Argentina. Instituto Franco‐Argentino sobre Estudios de Clima y sus Impactos; ArgentinaFil: Charo, M.. Ministerio de Defensa. Armada Argentina. Servicio de Hidrografía Naval. Departamento Oceanografía; ArgentinaFil: Romero, S. I.. Ministerio de Defensa. Armada Argentina. Servicio de Hidrografía Naval. Departamento Oceanografía; Argentin

Invisible work, unseen hazards: the health of women immigrant household service workers in Spain

BACKGROUND: Household service work has been largely absent from occupational health studies. We examine the occupational hazards and health effects identified by immigrant women household service workers. METHODS: Exploratory, descriptive study of 46 documented and undocumented immigrant women in household services in Spain, using a phenomenological approach. Data were collected between September 2006 and May 2007 through focus groups and semi-structured individual interviews. Data were separated for analysis by documentation status and sorted using a mixed-generation process. In a second phase of analysis, data on psychosocial hazards were organized using the Copenhagen Psychosocial Questionnaire as a guide. RESULTS: Informants reported a number of environmental, ergonomic and psychosocial hazards and corresponding health effects. Psychosocial hazards were especially strongly present in data. Data on reported hazards were similar by documentation status and varied by several emerging categories: whether participants were primarily cleaners or carers and whether they lived in or outside of the homes of their employers. Documentation status was relevant in terms of empowerment and bargaining, but did not appear to influence work tasks or exposure to hazards directly. CONCLUSIONS: Female immigrant household service workers are exposed to a variety of health hazards that could be acted upon by improved legislation, enforcement, and preventive workplace measures, which are discussed.Contract grant sponsor: Fondo de Investigaciones Sanitarias [Spanish Fund for Health Research]; Contract grant numbers: FIS PI050497, PI052334, PI061701, PI052202; Contract grant sponsor: Consejería de Empresa, Universidad y Ciencia de la Generalitat Valenciana [Valencian Regional Government, Ministry of Business, University and Science]; Contract grant number: AE/07/068; Contract grant sponsor: ARAI-AGAUR [Agency for the Management of University and Research Grants]; Contract grant number: 2006 ARAI 00020

Analysis of NPM1

Mutations of the nucleophosmin-1 (NPM1) gene in cytogenetically normal (CN) acute myeloid leukemia (AML) identify a group of patients with more favorable prognosis. NPM1 encodes three main alternatively spliced isoforms R1(B23.1), R2(B23.2), and R3(B23.3). The expression of splice variants R1, R2 and R3 were higher in AML patients compared to normal cells of healthy volunteers (HVs), although RNA-seq analysis revealed enhanced R2 expression also in less differentiated cells of HVs as well as in AML cells. The variant R2, which lacks exons 11 and 12 coding for the nucleolar localization domain, might behave similar to the mutant form of NPM1 (NPM1mut). In accordance, in CN-AML high R2 expression was associated with favorable impact on outcome. Moreover, functional studies showed nucleolar localization of the eGFP-NPM1 wildtype and cytoplasmic localization of the eGFP-NPM1 mut protein. While the eGFP-NPM1 R2 splice variant localized predominantly in the nucleoplasm, we also could detect cytoplasmic expression for the R2 variant. These results support a unique biological consequence of R2 overexpression and in part explain our clinical observation, where that high R2 variant expression was associated with a better prognosis in CN-AML patients