Discovering Novel Hearing Loss Genes: Roles For Esrp1 And Gas2 In Inner Ear Development And Auditory Function

Hearing loss is the most common form of congenital birth defect, affecting an estimated 35 million children worldwide. To date, nearly 100 genes have been identified which contribute to a deafness phenotype in humans, however, many cases remain in which a causative mutation has yet to be found. In addition, the exact mechanism by which hearing loss occurs in the presence of many of these mutations is still not understood. This is due, in part, to the complex nature of the development and function of the cochlear duct, the organ of hearing. The cochlea undergoes an intricate morphogenetic development and requires the proper specification and maintenance of dozens of different cell types in order to function correctly. In the mature duct, an interplay between mechanotransducing sensory hair cells, supporting pillar and Dieters\u27 cells, and generation of electrochemical potential by the stria vascularis are necessary to respond to sound stimuli. We utilized exome and RNA-sequencing experiments combined with mouse genetics in order to discover novel genes that play roles in cochlear development and function. Exome sequencing of families with profound hearing loss uncovered mutations in Epithelial Splicing Regulatory Protein 1 (ESRP1), a critical regulator of alternative mRNA splicing. Analysis of Esrp1 mutant mice revealed a shortened cochlear duct, delay in hair cell differentiation and maturation, and loss of the stria vascularis due to inappropriate Fgf ligand usage, stemming from an alternatively spliced receptor, in these cells. To identify additional regulators of inner ear development we performed an RNA-seq experiment comparing the gene expression profiles of control and Smoecko otic vesicles, which lack a cochlear duct. This generated a dataset of hundreds of cochlear enriched transcripts including Growth Arrest Specific 2 (Gas2) a cytoskeletal binding protein with the potential to act as a regulator of cochlear development. We generated a Gas2 null mouse line and discovered that these animals have severe hearing impairment likely due to defects in microtubule organization in the pillar cells. Taken together, these studies implicate Esrp1 and Gas2 as novel hearing loss genes that regulate aspects of cochlear development and function

A Review of \u3ci\u3eMinilimosina (Svarciella) \u3c/i\u3e Rohacek, with Descriptions of Fourteen New Species (Diptera: Sphaeroceridae)

A worldwide review of Minilimosina (Svarciella) Rohicek 1983, comprising 27 species, is provided, with data about the primary types, published descriptions and figures, synonyms and distribution including new records. A key to Svarciella species is presented and 14 new species are described and illustrated: M. floreni (Sweden), M. aterga, M. fanta, M. furculipexa, M. brachyptera, M. amphicuspa (all Nepal), M. triplex, M. comigera (both Malaysia), M. concinna, M. hastata (both Philippines), M. spinifera (Papua New Guinea), M. flagrella (Bismarck Is.), M. xanthosceles (Ecuador) and M. xestops (USA: Florida). M. furculisterna (Deeming 1969) is redescribed, including the previously undescribed female, and recorded from Japan. The female of M. unica (Papp 1973) is described for the first time and the species is recorded from northern Europe. M. hackmani (Rohicek 1977) is removed from synonymy with M. dissimilicosta (Spuler 1925) and synonymized under M. unica (Papp). M. paravitripennis (Papp 1973) is a new synonym of M. vitripennis (Zetterstedt 1847). The egg of M. concinna sp.n. is described and illustrated. The phylogeny and biogeography of world Svarciella species are discussed

A Review of \u3ci\u3eMinilimosina (Svarciella) \u3c/i\u3e Rohacek, with Descriptions of Fourteen New Species (Diptera: Sphaeroceridae)

A worldwide review of Minilimosina (Svarciella) Rohicek 1983, comprising 27 species, is provided, with data about the primary types, published descriptions and figures, synonyms and distribution including new records. A key to Svarciella species is presented and 14 new species are described and illustrated: M. floreni (Sweden), M. aterga, M. fanta, M. furculipexa, M. brachyptera, M. amphicuspa (all Nepal), M. triplex, M. comigera (both Malaysia), M. concinna, M. hastata (both Philippines), M. spinifera (Papua New Guinea), M. flagrella (Bismarck Is.), M. xanthosceles (Ecuador) and M. xestops (USA: Florida). M. furculisterna (Deeming 1969) is redescribed, including the previously undescribed female, and recorded from Japan. The female of M. unica (Papp 1973) is described for the first time and the species is recorded from northern Europe. M. hackmani (Rohicek 1977) is removed from synonymy with M. dissimilicosta (Spuler 1925) and synonymized under M. unica (Papp). M. paravitripennis (Papp 1973) is a new synonym of M. vitripennis (Zetterstedt 1847). The egg of M. concinna sp.n. is described and illustrated. The phylogeny and biogeography of world Svarciella species are discussed

Ultrasonographic findings in patients with abdominal symptoms or trauma presenting to an emergency room in rural Tanzania

BACKGROUND: Frequencies of ultrasonographic findings and diagnoses in emergency departments in sub-Saharan Africa are unknown. This study aimed to describe the frequencies of different sonographic findings and diagnoses found in patients with abdominal symptoms or trauma presenting to a rural referral hospital in Tanzania. METHODS: In this prospective observational study, we consecutively enrolled patients with abdominal symptoms or trauma triaged to the emergency room of the Saint Francis Referral Hospital, Ifakara. Patients with abdominal symptoms received an abdominal ultrasound. Patients with an abdominal or thoracic trauma received an Extended Focused Assessment with Ultrasound in Trauma (eFAST). RESULTS: From July 1st 2020 to June 30th 2021, a total of 88838 patients attended the emergency department, of which 7590 patients were triaged as 'very urgent' and were seen at the emergency room. A total of 1130 patients with abdominal symptoms received an ultrasound. The most frequent findings were abnormalities of the uterus or adnexa in 409/754 females (54.2%) and abdominal free fluid in 368 (32.6%) patients; no abnormality was found in 150 (13.5%) patients. A tumour in the abdomen or pelvis was found in 183 (16.2%) patients, an intrauterine pregnancy in 129/754 (17.1%) females, complete or incomplete abortion in 96 (12.7%), and a ruptured ectopic pregnancy in 32 (4.2%) females. In males, most common diagnosis was intestinal obstruction in 54/376 (14.4%), and splenomegaly in 42 (11.2%). Of 1556 trauma patients, 283 (18.1%) received an eFAST, and 53 (18.7%) had positive findings. A total of 27 (9.4%) trauma patients and 51 (4.5%) non-trauma patients were sent directly to the operating theatre. CONCLUSION: In this study, ultrasound examination revealed abnormal findings for the majority of patients with non-traumatic abdominal symptoms. Building up capacity to provide diagnostic ultrasound is a promising strategy to improve emergency services, especially in a setting where diagnostic modalities are limited

Modelação e concepção da carroçaria do veículo eléctrico ecológico (VEECO)

Neste trabalho aborda-se o desenvolvimento da carroçaria do Veículo Eléctrico Ecológico – VEECO recorrendo a tecnologias assistidas por computador. Devido à impossibilidade de abranger toda a temática das tecnologias assistidas por computador, associadas ao desenvolvimento de uma carroçaria automóvel, o foco deste trabalho assenta no processo de obtenção de um modelo digital válido e no estudo do desempenho aerodinâmico da carroçaria. A existência de um modelo digital válido é a base de qualquer processo de desenvolvimento associado a tecnologias assistidas por computador. Neste sentido, numa primeira etapa, foram aplicadas e desenvolvidas técnicas e metodologias que permitem o desenvolvimento de uma carroçaria desde a sua fase de “design” até à obtenção de um modelo digital CAD. Estas abrangem a conversão e importação de dados, a realização de engenharia inversa, a construção/reconstrução CAD em CATIA V5 e a preparação/correcção de modelos CAD para a análise numérica. Numa segunda etapa realizou-se o estudo da aerodinâmica exterior da carroçaria, recorrendo à ferramenta de análise computacional de fluidos (CFD) Flow Simulation da CosmosFloworks integrado no programa SolidWorks 2010. Associado à temática do estudo aerodinâmico e devido à elevada importância da validação dos resultados numéricos por meio de dados experimentais, foi realizado o estudo de análise dimensional que permite a realização de ensaios experimentais à escala, bem como a análise dos resultados experimentais obtidos.In the present work the development of the body of the Ecological Electric Vehicle – VEECO using computer-assisted technologies is addressed. Due to the impossibility to address the entire subject of computer-assisted technologies, in the development of a road vehicle body, the focus of this work lies in obtaining a valid digital model and in the study of the aerodynamic performance of the body. The existence of a valid digital model is the starting point for any development process associated with computer-assisted technologies. In this sense, in a first step, techniques and methodologies were applied and developed that enable the development of a body from its design phase until the obtainment of a digital CAD model. These include the conversion and importing of data, reverse engineering, the CAD construction/reconstruction in CATIA V5 and the preparation/correction of CAD models for the numerical analysis. In a second step, the external aerodynamics study of the body was performed, using the computational fluid dynamics (CFD) tool Flow Simulation from CosmosFloworks integrated in the software SolidWorks 2010. Associated with the thematic of aerodynamic analysis and the importance of validating the numerical results with experimental data, a dimensional analysis which allows to conduct experimental tests with scale models was performed, as well as the analysis of the obtained experimental results

Ordering CT pulmonary angiography to exclude pulmonary embolism: defense versus evidence in the emergency room

Purpose: To identify reasons for ordering computed tomography pulmonary angiography (CTPA), to identify the frequency of reasons for CTPA reflecting defensive behavior and evidence-based behavior, and to identify the impact of defensive medicine and of training about diagnosing pulmonary embolism (PE) on positive results of CTPA. Methods: Physicians in the emergency department of a tertiary care hospital completed a questionnaire before CTPA after being trained about diagnosing PE and completing questionnaires. Results: Nine hundred patients received a CTPA during 3years. For 328 CTPAs performed during the 1-year study period, 140 (43%) questionnaires were completed. The most frequent reasons for ordering a CTPA were to confirm/rule out PE (93%), elevated D-dimers (66%), fear of missing PE (55%), and Wells/simplified revised Geneva score (53%). A positive answer for "fear of missing PE” was inversely associated with positive CTPA (OR 0.36, 95% CI 0.14-0.92, p=0.033), and "Wells/simplified revised Geneva score” was associated with positive CTPA (OR 3.28, 95% CI 1.24-8.68, p=0.017). The proportion of positive CTPA was higher if a questionnaire was completed, compared to the 2-year comparison period (26.4 vs. 14.5%, OR 2.12, 95% CI 1.36-3.29, p<0.001). The proportion of positive CTPA was non-significantly higher during the study period than during the comparison period (19.2 vs. 14.5%, OR 1.40, 95% CI 0.98-2.0, p=0.067). Conclusion: Reasons for CTPA reflecting defensive behavior—such as "fear of missing PE”—were frequent, and were associated with a decreased odds of positive CTPA. Defensive behavior might be modifiable by training in using guideline

Electrical valley filtering in transition metal dichalcogenides

This work investigates the feasibility of electrical valley filtering for holes in transition metal dichalcogenides. We look specifically into the scheme that utilizes a potential barrier to produce valley-dependent tunneling rates, and perform the study with both a k.p based analytic method and a recursive Green's function based numerical method. The study yields the transmission coefficient as a function of incident energy and transverse wave vector, for holes going through lateral quantum barriers oriented in either armchair or zigzag directions, in both homogeneous and heterogeneous systems. The main findings are the following: 1) the tunneling current valley polarization increases with increasing barrier width or height, 2) both the valley-orbit interaction and band structure warping contribute to valley-dependent tunneling, with the former contribution being manifest in structures with asymmetric potential barriers, and the latter being orientation-dependent and reaching maximum for transmission in the armchair direction, and 3) for transmission ~ 0.1, a tunneling current valley polarization of the order of 10% can be achieved.Comment: 12 pages, 8 figure

Erratum to “The Challenge of Triaging Chest Pain Patients: The Bernese University Hospital Experience”

Accurate diagnosis of the causes of chest pain and dyspnea remain challenging. In this preliminary observational study with a 5-year follow-up, we attempted to find a simplified approach to selecting patients with chest pain needing immediate care based on the initial evaluation in ED. During a 24-month period were randomly selected 301 patients and a conditional inference tree (CIT) was used as the basis of the prognostic rule. Common diagnoses were musculoskeletal chest pain (27%), ACS (19%) and panic attack (12%). Using variables of ACS symptoms we estimated the likelihood of ACS based on a CIT to be high at 91% (32), low at 4% (198) and intermediate at 20.5–40% in (71) patients. Coronary catheterization was performed within 24 hours in 91% of the patients with ACS. A culprit lesion was found in 79%. Follow-up (median 4.2 years) information was available for 70% of the patients. Of the 164 patients without ACS who were followed up, 5 were treated with revascularization for stable angina pectoris, 2 were treated with revascularization for myocardial infarction, and 25 died. Although a simple triage decision tree could theoretically help to efficient select patients needing immediate care we need also to be vigilant for those presenting with atypical symptoms

The Chronic Diseases Clinic of Ifakara (CDCI)- establishing a model clinic for chronic care delivery in rural sub-Saharan Africa

The rollout of antiretroviral drugs in sub-Saharan Africa to address the huge health impact of the HIV pandemic has been one of the largest projects undertaken in medical history and is an unprecedented medical success story. However, the path has been and still is characterized by many far reaching implementational challenges. Here, we report on the building and maintaining of a role model clinic in Ifakara, rural Southwestern Tanzania, within a collaborative project to support HIV services within the national program, training for staff and integrated research to better understand local needs and improve patients' outcomes