Congenital hearing loss in Malta : a survey

The congenitally deaf infant who acquires deafness prior to development of language present special problems when compared to other hearing impaired individuals. This is because both the development of speech and of language depends on adequate hearing. As speech and language are our prime means of communication, the congenitally deaf child is automatically also handicapped in his psychological development, social adaptation and work adaptability. The authors reviewed cases of congenital hearing loss presenting on a 20 year period to establish the incidence of congenital hearing impairment in the Maltese islands; to determine the common causes; to highlight any difficulties in early diagnosis and management of these children.peer-reviewe

Nursing Home Regulations Redefined: Implications for Providers

The Centers for Medicare and Medicaid Services (CMS) finalized a comprehensive update to nursing home requirements of participation in October 2016. Nearly 10,000 public comments were received regarding the proposed rule, and CMS made multiple modifications based on comments from providers, advocacy organizations, and others before issuing the final rule. The final rule describing nursing home requirements of participation modernizes nursing home regulation. It is being implemented in three phases—beginning in November 2016, November 2017, and November 2019. There are multiple provisions that have implications for clinicians caring for nursing home residents, particularly in terms of management of infections, medication prescribing and monitoring, and delegation of medical orders

Determination of the scope of the experimental-calculation method for measuring the touch voltage

The work is devoted to the improvement of methods for determining the normalized parameters of the grounding system (GS) of operating power stations and substations. The aim of the work is determination of the scope of the experimental-calculated method for measuring the touch voltage, depending on short-circuit (SC) current value for the given dimensions of the GS and the type of soil. Methodology. The study analyzed the non-linear effect of the SC current value on the touch voltage, taking into account such factors as the GS size and the soil type. The calculation used statistical data on the GS size and the characteristics of the soil obtained by monitoring the GS state of 585 operating electrical substations with a voltage class of 110-750 kV using the induction method and the method of vertical soil sounding, respectively. For the calculation, a mathematical model of a non-equipotential GS located in a three-layer semiconductor space with plane-parallel boundaries was used, this model was developed using the method of integro-differential equations. Results. To determine the scope of the method, in this work it is proposed to use the linearity criterion, which is determined due to the ratio of the constant of reduced touch voltage to the current value. The example shows the method for determining the threshold minimum and maximum values of the measuring current of the soil, in the range between which the measurements by experimental-calculated methods are impossible. A table of threshold current values has been formed and recommendations have been developed on the possibility of using experimental-measuring methods for determining the touch voltage depending on the GS size and soil characteristics.Метою роботи є визначення області застосування експериментально-розрахункового методу вимірювання напруги дотику в залежності від значення струму короткого замикання для заданих розмірів заземлювального пристрою (ЗП) та типу ґрунту. В дослідженні було проаналізовано нелінійний вплив величини струму КЗ на напругу дотику з урахуванням таких факторів як розмір ЗП та тип ґрунту. Для розрахунку була використана математична модель нееквіпотенційного ЗП, розташованого у тришаровому напівпровідному просторі з плоско-паралельними границями поділу, що була розроблена за допомогою методу інтегро-диференційних рівнянь. Для визначення області застосування методу в роботі запропоновано використовувати критерій лінійності, який визначається через відношення сталої приведеної напруги дотику до поточного значення. Сформовано таблицю значень порогових струмів та розроблено рекомендації щодо можливості використання експериментально-вимірювальних методів визначення напруги дотику в залежності від розміру ЗП та характеристик ґрунту

Method of integro-differential equations for interpreting the results of vertical electrical sounding of the soil

The paper is devoted to the problem of determining the geoelectric structure of the soil within the procedure of testing the grounding arrangements of existing power plants and substations to the required depth in conditions of dense development. To solve the problem, it was proposed to use the Schlumbergers method , which has a greater sounding depth compared to the Wenner electrode array. The purpose of the work is to develop a mathematical model for interpreting the results of soil sounding by the Schlumberger method in the form of a four-layer geoelectric structure. Methodology. To construct a mathematical model, it is proposed to use the solution of a particular problem about the field of a point current source, which, like the observation point, is located in the first layer of a four-layer soil. Based on this expressions, a system of linear algebraic equations of the 7-th order with respect to the unknown coefficients ai and bi was compiled. On the basis of its analytical solution, an expression for the potential of the electric field was obtained for conducting VES (the point current source and the observation point are located only on the soil surface). Results. Comparison of the results of soil sounding by the Schlumberger installation and the interpretation of its results for the same points shows a sufficient degree of approximation: the maximum relative error does not exceed 9.7 % (for the second point), and the average relative error is 3.6 %. Originality. Based on the obtained expression, a test version of the program was implemented in Visual Basic for Applications to interpret the results of VES by the Schlumberger method. To check the obtained expressions, the interpretation of the VES results was carried out on the territory of a 150 kV substation of one of the mining and processing plants in the city of Kriviy Rih. Practical significance. The developed mathematical model will make it possible to increase the sounding depth, and, consequently, the accuracy of determining the standardized parameters of the grounding arrangements of power stations and substations.Робота присвячена проблематиці визначення геоелектричної структури ґрунту в межах випробування заземлювальних пристроїв діючих електричних станцій та підстанцій на необхідну глибину в умовах щільної забудови. Для вирішення проблеми запропоновано використати установку Шлюмберже, яка має більшу глибину зондування у порівнянні з установкою Веннера. За допомогою методів інтегро-диференційних рівнянь було отримано аналітичні вирази для інтерпретації результатів зондування ґрунту установкою Шлюмберже у випадку чотиришарового ґрунту. Для перевірки отриманих виразів була проведена інтерпретація результатів вертикального електричного зондування на території підстанції 150 кВ одного з гірничо-збагачувальних комбінатів: максимальна відносна похибка не перевищує 9,7 %, а середня – 3,6 %

Deregulation of the phosphatase, PP2A is a common event in breast cancer, predicting sensitivity to FTY720

We would like to thank Professor Andrew Hanby, Professor Valerie Speirs and Dr Thomas A Hughes for the breast cancer cell lines used in this study. This research was supported by the Faculty of Medicine and Surgery, University of Malta.Background: The most commonly used biomarkers to predict the response of breast cancer patients to therapy are the oestrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2). Patients positive for these biomarkers are eligible for specific therapies such as endocrine treatment in the event of ER and PgR positivity, and the monoclonal antibody, trastuzumab, in the case of HER2-positive patients. Patients who are negative for these three biomarkers, the so-called triple negatives, however, derive little benefit from such therapies and are associated with a worse prognosis. Deregulation of the protein serine/threonine phosphatase type 2A (PP2A) and its regulatory subunits is a common event in breast cancer, providing a possible target for therapy. Methods: The data portal, cBioPortal for Cancer Genomics was used to investigate the incidence of conditions that are associated with low phosphatase activity. Four (4) adherent human breast cancer cell lines, MDA-MB-468, MDA-MB-436, Hs578T and BT-20 were cultured to assess their viability when exposed to various dosages of rapamycin or FTY720. In addition, RNA was extracted and cDNA was synthesised to amplify the coding sequence of PPP2CA. Amplification was followed by high-resolution melting to identify variations. Results and conclusion: The sequence of PPP2CA was found to be conserved across a diverse panel of solid tumour and haematological cell lines, suggesting that low expression of PPP2CA and differential binding of inhibitory PPP2CA regulators are the main mechanisms of PP2A deregulation. Interestingly, the cBioPortal for Cancer Genomics shows that PP2A is deregulated in 59.6% of basal breast tumours. Viability assays performed to determine the sensitivity of a panel of breast cancer cell lines to FTY720, a PP2A activator, indicated that cell lines associated with ER loss are sensitive to lower doses of FTY720. The subset of patients with suppressed PP2A activity is potentially eligible for treatment using therapies which target the PI3K/AKT/mTOR pathway, such as phosphatase activators.peer-reviewe

Simulation of electromagnetic processes in the grounding system with a short circuit in the operating high-voltage substation

The aim of the work is a test of the developed mathematical model of electromagnetic processes of short circuit and approbation of the created software complex «LiGro» on its basis for the existing grounding system located in three-layer soil. Methodology. To improve the accuracy of calculating the normalized parameters of operating power stations and substations, the authors developed the «LiGro» software package based on the expressions obtained in for calculating the potential of the electric field of a non-equipotential grounding system (GS). To monitor the state and assess the efficiency of the GS of operating power facilities, the electromagnetic diagnostics is used. The topology of the GS was determined with the induction method by complex KNTR-1, the geoelectric structure of the soil was determined by the method of vertical electrical sounding using the Wenner installation, the interpretation of the sounding results was made by the «VEZ-4A» program. The calculation results show that for the selected substation, the model developed in the «LiGro» complex has a deviation δ2 from the experimental values Ut by an average of 8,2 %, and the model implemented in Grounding 1.0 (IEEE model) δ1 is 17,2 %. Originality. The results of the study confirm the adequacy of the developed GS model in the «LiGro» complex based on a three-layer soil model, with the experimental values of the touch voltage obtained by simulating a single-phase ground fault on a real GS in operation. The first time was made approbation of the «LiGro» software package when performing the EMD of the GS of an operating substation with a voltage class of 150 kV. Practical significance. The program software can be used by special measuring’s laboratory to determining electrical safety parameters: touch voltage, GS voltage, and GS resistance. Метою роботи є перевірка розробленої математичної моделі електромагнітних процесів короткого замикання та апробація створеного програмного комплексу «LiGro на її основі для існуючого заземлювального пристрою (ЗП), який розташовано в тришаровому ґрунті. Перевірка практичного застосування була виконана на діючий підстанції класом напруги 150 кВ з використанням вдосконаленої методики електромагнітної діагностики. Топологія ЗП була визначена індукційним методом за допомогою приладу KNTR-1, параметри ґрунту визначені чотириелектродною симетричною установкою за схемою Веннера методом вертикального електричного зондування, інтерпретація результатів зондування виконана спеціалізованою програмою VEZ-4A. Результати порівняння розрахунку показують, що для обраної підстанції модель розроблена в комплексі LiGro має відхилення від експериментальних значень в середньому на 8,2 %, а модель реалізована в Grounding 1.0 (IEEE model) – 17,2 %. Виконано розрахунок нормованих параметрів ЗП в режимі короткого замикання: напругу дотику, опір ЗП та напругу на ЗП. Встановлено, що вони не перевищують допустимого значення. Проаналізовано переваги розрахункового комплексу у порівнянні з аналогами. Отримані результати дозволяють виконати повномасштабне впровадження програмного комплексу в діагностику стану ЗП.&nbsp

Predictive markers in cancer patient diagnosis, classification and prediction of therapy outcome using leukaemia as a model

The characterisation of the molecular mechanism of disease allows classification of patients into subtypes and potentially identifies specific targets for therapeutic intervention. Tyrosine kinase mutations are central to specific targeted therapy. Investigation of kinase deregulation within particular patient groups, has led to identification of mutant tyrosine kinases associated with disease progression and therapy modulation. Biomarker-specific therapies emerged, taking a leading role in guided-therapy. The extensive use of the specific kinase inhibitors and the longevity of the treatment protocols due to the uncertainty of residual disease, gave rise to new challenges, namely secondary resistance to therapy. Although there are various mechanisms of acquired resistance, mutations in the drug target itself play a dominant role.peer-reviewe

Integrating SpyCatcher/SpyTag covalent fusion technology into phage display workflows for rapid antibody discovery.

An early bottleneck in the rapid isolation of new antibody fragment binders using in vitro library approaches is the inertia encountered in acquiring and preparing soluble antigen fragments. In this report, we describe a simple, yet powerful strategy that exploits the properties of the SpyCatcher/SpyTag (SpyC/SpyT) covalent interaction to improve substantially the speed and efficiency in obtaining functional antibody clones of interest. We demonstrate that SpyC has broad utility as a protein-fusion tag partner in a eukaryotic expression/secretion context, retaining its functionality and permitting the direct, selective capture and immobilization of soluble antigen fusions using solid phase media coated with a synthetic modified SpyT peptide reagent. In addition, we show that the expressed SpyC-antigen format is highly compatible with downstream antibody phage display selection and screening procedures, requiring minimal post-expression handling with no sample modifications. To illustrate the potential of the approach, we have isolated several fully human germline scFvs that selectively recognize therapeutically relevant native cell surface tumor antigens in various in vitro cell-based assay contexts