DNA Based Biosensor in Diagnosis: A Review

DNA Based Biosensor in Diagnosis: A Review The advent of fast and easy DNA testing has given the space for the Science to develop small and easy-to-handle equipments called Biosensors. DNA based biosensors have been proven very useful and are accorded with much importance in detecting the target genes responsible for diseases. This article enlists different types of biosensors, their basic principle of operating system, the preparation of DNA microarrays, lab-on-a-chip and their role in diseases diagnosis. DNA biosensors provide swift, sensitive, selective, simple and economical detection of DNA hybridization. New strategies for DNA biosensor are enumerated and are used meticulously in recent trends and for future directions. Carbon nanotubes (CNTs) amplify the electrochemical signal when used with DNA hybridization. Electrochemical, piezoelectric, SPR, optical DNA biosensors are used to detect various viruses like hepatitis virus, HCMV, HIV, orthopox virus etc. and also for the diagnosis of various diseases like cancer, tube rculosis, COPD, genetic diseases (sickle cell anemia i.e. due to single point gene mutation), cystic fibrosis, diabetes etc. The methodologies of detecting such diseases using different types of DNA based biosensors and gene chips are described in this article. PCR free DNA chips, cell- omic sensors and nanosensor are emerging tools in the field of diagnosis. Recent advances in developing such devices provide myriads of new opportunities for DNA diagnostics. Introduction A rapidly developing area of biotechnology arousing intense scientist interest is that of biosensor. Biosensor has become popular in the field of food analysis [1], bioterrorism [3], environmental [2-3] and in the area of human health monitoring and diagnostics [4-6]. Recent advances are being mad in all areas of biosensors technology. Presently, most fascinating and prospective sensors are immunosensors based on affinity reactions between antibody and antigens and DNA biosensors based on the hybridization between DNA probes and their complementary DNA strands. In general, biosensor is an analytical device which employs biological recognition properties for a selective analysis. Such sensors combine a biological element with a physiochemical transducer for the electronic signal output which is proportional to the concentration of analytes [7]. A basic biosensor assembly includes a biological element, transducer and detector. The sensing material may be antibodies, enzymes, whole cell or nucleic acids that form a recognition layer which is integrated with the transducer via immobilization by cross linking, adsorption or covalent binding. Transducers may be amperometric (measuring the current at constant potential) [8], potentiometric (measuring the potential at constant current) [9], piezoelectric (measuring the changes in mass), thermal (measuring the changes in temperature) [10] or optical (detects changes in transmission of light) [11]. The interaction between the analyte and the biological material, used in biosensors may be of two types: a) Bioaffinity sensors: depend on the selective and specific attachment of the target molecule to the surface-attached ligand partner (e.g. antibodies, nucleic acids). b) Biocatalytic sensors: an immobilized enzyme is used as a tool to recognize the target substrate (sensor strips with immobilized glucose oxidase used for personal monitoring of diabetes). A number of steps, much labor, time and costly instruments are required in usual analytical technique whereas biosensors are economical, fast and simple and can be used in small laboratories and hospitals of remote areas which are devoid of sophisticated instruments facilities. DNA Biosensors Nucleic acid recognition process is the basis of DNA Biosensors. These are being developed with a rapid pace with an ambition for inexpensive testing for genetic and infectious disease and for detecting DNA damage and interactions. The study of gene polymorphisms and the analysis of gene sequences play a fundamental role in rapid detection of genetic mutations, opens up new opportunities for reliable diagnosis even before any symptoms of a disease appear. Thus recent advances in developing such devices offer the opportunities for DNA diagnostics. DNA biosensors are made by immobilizing single stranded (ss) DNA probes on different transducers for measuring the hybridization between the DNA probes and their complementary DNA strands [12-13]. The current methods to identify specific DNA sequence in Biological samples depends on the isolation of double stranded (ds) DNA and further polymerase chain reaction (PCR) to amplify the target sequence of DNA. The PCR product is then subjected to electrophoresis or adsorbed onto a suitable membrane and exposed to a solution containing DNA probe. Surface Chemistry and Biochemistry The immobilization of DNA probe onto the transducer plays an important role in the performance of the DNA Biosensor. It should be in well-defined probe orientation and should be readily accessible to the target. The mode of immobilization is the determining factor for the type of environment of probes that are immobilized at the solid surface. On the basis of nature of physical transducer, various schemes can be opted for the DNA probes attachment to the surface such as thiolated DNA utilisation for self binding onto gold transducers, the formation of a complex by the use of biotylated DNA with a surface-confined strepavidin or avidin, covalent binding to the gold surface through functional alkanethiol-based monolayer and coupling covalently (carbodiimide) to the functional groups on carbon electrodes or adsorption onto carbon surfaces. Introduction of peptide nucleic acid (PNA) has paved way for many exciting and new opportunities to DNA biosensors. Peptide Nucleic Acid is a DNA mimic, the only difference is that the sugar-phosphate bone is replaced by a pseudo-peptide one. Like use of surface-confined PNA recognition layers provides remarkable sequence specificity on DNA biosensors and offers other advantages. DNA dendrimers may also be utilized for imparting extreme sensitivity onto DNA Biosensors. By shape, these are tree-like superstructures which possess numerous ss arms that are able to hybridize to their complementary DNA sequence. The immobilization of these dendritic nucleic acids onto physical transducer gives an amplified response [14]. Recent advances in the field of biomolecular techniques may be used to design new generation miniaturized biosensor. Types of DNA based Biosensors 1. Optical Type Fiber optics Biological Element Laser Interferometry Transducer DNA Advantages Optical fiber Highly sensitive Disadvantages Expensive equipment and not portable turbidity interference 2. Electrochemical Type Potentiometric Biological Element Conductometric Transducer Amperometric DNA Advantages Carbon paste electrodes Cheap, Fast Limitations Interference of highly buffered solution 3. Piezoelectric Type DNA Biological Element Quartz Crystals Advantages highly sensitive, Fast 4. DNA chips DNA Quantitative Optical DNA based Biosensor Optical methods are the most commonly used for the detection of analytes. DNA optical biosensors are based on a fiber optic which transduces the emission signal to a fluorescent label and that can carry light from one region to another through a series of internal inflections. The methodology of fiber-optic DNA bio-sensors involves placing of a single stranded DNA probe at the ending-site of fiber and assessing the fluorescent changes resulting from the combination of a fluorescent indicator with the double stranded DNA hybrid [15 16]. The first DNA optical bio-sensors were developed by Krull and Co workers using fluorescent indicator ethidium bromide. A fiber-optic DNA sensor array was developed by Watts group for the detection of multiple DNA sequences at one time [17]. The hybridization of fluorescent labeled complementary oligonucleotides was assessed by observing the increase in fluorescence. A real label free optical detection of DNA hybridization can be offered by a different type of optical transduction based on evanescent wave devices. The different types of optical biosensors include: 1.1 Surface Plasmon Resonance (SPR) It is a quantum optical electrical phenomenon based on the interaction of light with metal surface. Only at specific resonance wavelength of light, the energy carried by photons of light is transferred to packets of electrons (photons) on a metal surface [17]. These biosensors depend on change in surface optical properties (change in resonance angle because of alteration in interfacial refractive index) which results from the surface binding reaction. Thus, these devices integrate the simplicity of SPR with the sensitivity and specificity of wave guiding devices. The SPR signal that is expressed in resonance units is therefore a measure of mass concentration at the senor chip surface [18-20]. 1.2 Molecular Beacons (MBs) MBs are oligonucleotides possessing a stem and loop structure that are labeled with a quencher at one end and a fluorophore on the other end of the stem that converts into fluorescent upon hybridization. MB probes possess high sensitivity and specificity and direct monitoring capability. A biotinylated molecular beacon probe was developed to prepare a DNA sensor using a bridge structure. MB was biotinylated at quencher site of the stem and linked on a glass through streptavidin that act as a bridge between MB and glass matrix. The fluorescence change was measured by confirmation change of MB in the presence of complementary target DNA [21-23]. Quantum Dot It is an ultra sensitive nanosensor based on fluorescence resonance energy transfer (FREET) that can detect very low concentration of DNA. In these neon sensors, quantum dots (QDs) are linked to specific DNA probes to capture target DNA. The target DNA strand binds to a fluorescent dye (Fluorophore) labeled reporter strand and thus forming FREET donor acceptor assembly. Quantum dot also functions as target concentrator as well as FREET energy donor [24]. DNA nanosensor contains two target specific DNA probes i.e. reporter and capture probe. The reporter probe is labeled with fluorophore whereas capture probe is labeled with biotin that binds with streptavidin conjugated with QD [25]. The fluorophore acceptor and QD donor in close proximity produce fluorescence from acceptor by means of FREET on illumination of the donor. The presence of target DNA is indicated by the detection of acceptor emission. The un-hybridized probe does not give fluorescence. The CdSe Zns core shell nanocrys tal can be used as donor and Cy5 (fluorophore) as acceptor for developing QD based DNA nanosensors [25]. For this type of optical bio sensors fluorescent dyes used as standard labels are very expensive and can rapidly photo bleach. An alternate used is chemiluncinscence format, which overcomes the use of fluorescent dyes. A Fiber-optic DNA biosensor array A new method of preparing the fiber-optic DNA biosensor and its array for the simultaneous detection of multiple genes is described. The optical fibers were made into fiber-optic DNA biosensors by adsorbing and immobilizing the oligonucleotide probe on its end but were first treated with poly-l-lysine. The fiber-optic DNA biosensor array was well prepared by assembling the fiber-optic DNA biosensors in a bundle in which each fiber carried a different DNA probe. Hybridization of fluorescent- labeled cDNA of Rb1 gene, N-ras gene and Rb1 p53 gene to the DNA array was monitored CCD camera. A good result was achieved [61]. 2. Electrochemical DNA Bio sensors These are very useful devices for sequence specific biosensing of DNA. The inherent miniaturization of such devices and advance micro fabrication technology make them excellent tool to diagnose DNA. DNA hybridization is detected electrochemically by monitoring the current response at fixed potential. Detection of hybridization is also commonly done through the increased current of a redox indicator or from other changes induced by hybridization in electrochemical parameters such as capacitance or conductivity [26-28]. The discovery of carbon nano tubes (CNTs) plays an important role in development of electrochemical DNA sensors. Various CNT based electrochemical are developed because the combination of unique electrical, thermal, chemical, mechanical and 3-D spatial properties of CNTs with DNA hybridization offers the possibility of creating DNA bio sensors with specificity, simplicity, high sensitivity and multiplexing. Two major groups in which CNTs divided are single walled CNTs (SWCNTs) that are comprised of a single graphite sheet rolled with a tube and multi walled CNTs (MWCNTs) that are concentric closed graphite tubes [29]. CNT enables immobilization of DNA molecules and also used as powerful amplifier to amplify signal transduction of hybridization [30]. Two types are generally used to immobilize the CNT on electrodes aligned and non-aligned. Two approaches are generally used for the immobilization of bio molecules onto CNTs that are non covalent attachment (physical absorption) and covalent binding (some cross linker agents (1-ethyl 3-3 dimethylaminopropyl) carbodilimide hydrochloride (EDC)/N-hydroxysuccinimide (NHS)] or affinity binding (avidin biotin interaction). CNT also act as novel indicator of hybridization. The application of arrayed CNT into DNA chip requires small amount of sample and development of CNT base biosensor has an important role in DNA based diagnostics in hospitals or at home [30]. Various methods are used for immobilizations step i.e. for attaching the DNA probe onto the solid surface that are (a) the use of thiolated DNA probe for self assembled monolayers (SEM) onto gold transducers by covalently bonding to the gold surface through functional alkanethiol based monolayers.(b) Attachment of biotinylated DNA probe through biotin avidin interaction on electrode surface for e.g. avidin modified polyaniline electro chemically deposited onto a Pt disc electrode for direct detection of E. Coli by immobility a 5 biotin labeled probe using a differential pulse Voltametric technique in the presence of methylene blue as an DNA hybridization indicator [31,32]. The electrochemical DNA biosensors may be labeled free and labeled based. Label Free In this direct detection technique the target molecule does not need to be labeled [27]. The elimination of labeling steps simplifies the readout the speed and ease of nucleic acid assays. Thus recently increased attention has been accorded to new label free electrochemical detection schemes. There is a possibility in exploiting the changes in DNAs intrinsic electroactivity (Guanine oxidation peak of hybridization). To deal with the drawbacks of the probe sequences i.e. absence of G, guanines were substituted by inosine residues (pairing with C) and detection of hybridization was done through the target DNA guanine signal. The change in the guanine oxidation and intrinsic DNA redox signals detects the chemical and physical damage [33]. Label Based In label based electrochemical biosensor specific organic dyes, enzymes or metal complexes are used for hybridization detection. Redox active molecules such as methylene blue, dacinomycin that is inserted between the dsDNA and gives signal which is used for detecting hybridization [26] (e.g. of two commercialized DNA chips based on redox active molecules are eSensor TM produced by Motorola life sciences [34], Inc. and Genlyser TM by Toshiba)[35]. Piezoelectric DNA Biosensor These are the mass sensitive devices rely on quartz crystal that oscillate at a defined frequency when oscillation voltage is applied. Increased attention has been given to piezoelectric method due to their simplicity, cost, sensitivity and real time label free detection. The quartz crystal microbalance is an extremely sensitive piezoelectric device that monitors the hybridization events. These biosensors DNA probe is immobilized on the surface of oscillation crystal. The increased mass due to hybridization reaction results in change in oscillating frequency [36-37]. A Piezoelectric sensor for determination of genetically modified soyabean roundup ready [RR soyabean] by immobilizing probe related to 5-enolpyrllvylshikimate 3-phosphate synthase (EPSPS) gene onto gold piezoelectrodes [38]. For detecting a point mutation in a human gene (apolipoprotein-E polymorphism) a combination of DNA piezoelectric biosensor and PCR was developed by immobilizing biotinylated probe on the streptavidin coated gold surface of quartz crystal. The hybridization probes with complementary, non-complementary and mismatched DNA of synthetic as well as amplified PCR samples from human blood DNA was taken out and the device was able to distinguish polymorphism [39]. Colorimetric or Strip type DNA sensor Using these sensors the direct detection of DNA hybridization is possible [40-42]. The dry-reagent strip type biosensor has been developed for visual detection of double stranded DNA within a short time [43]. Oligonucleotides conjugated gold particle is used as probe. The main advantage of these biosensors is not requiring any instruments, multiple incubation and washing steps. Integral part of strip consists of gold particles, with oligo (dT) attached to their surface. Biotinylated PCR products are hybridized with poly (dA) tailed oligo, switched to the top of strip and immersed in the appropriate buffer. With the migration of buffer in upward direction, the nanoparticles that are linked through target DNA through poly (dA/dT) hybridization are rehydrated. Immobilized streptavidin then capture the hybrid in the controlled zone of the strip. The test is 8-10 times more sensitive than ethidium bromide in agarose gel electrophoresis. The detection limit is abysmally low of 2 fmol of amplified DNA products. DNA Biochips Microarrays, DNA arrays, gene chips or biochips are same terminology often being intermixed. DNA microarrays are small, solid supports which themselves are usually microscopic slides, but can also be silicon chips or nylon membranes onto which the sequences from thousands of different genes are immobilized, or attached, at fixed locations. The DNA may be spotted, or synthesized directly onto the support. DNA microarrays detect the change in gene expression levels, genomic gained and losses, mutations in DNA and infectious agents, diagnosis of genetic diseases, drug screening or forensic analysis. Developing the methods for detecting target hybridization, designing probe arrays, data analysis and reconstructing the target sequence are required for successful implementation of DNA chip technology. Such array technology thus forms the basis of integration of molecular biology, surface and analytical chemistry, advanced micro fabrication, robotics, software and automation. In this technique, RNA extracted from two samples are labeled with two different fluorochromes (generally the green cyanine 3 and the red cyanine 5 (Cy3, Cy5)) before being hybridized to a biochip consisting of large numbers of cDNAs/oligonucleotides arranged orderly onto a glass microscopic slide. After hybridization, a scanner records excitation of the two fluorochromes at given wavelengths and the intensity of the fluorescence emission signals that is proportional to transcript levels in the biological samples. The data is analyzed using specific software that enables clustering of genes with similar expression patterns, with the assumption that they share common biological functions [33, 44]. A new ultrasensitive electronic sensor has been developed by Singapore scientists that would speed up effectively DNA testing for disease diagnosis and biological research. The novel electronic sensor array would be faster, accurate and cost-efficient. Excellent sensitivity has been shown by the Nanogap Sensor Array in detecting the trace amounts of DNA. By saving time and cutting expenses, newly developed Nanogap Sensor Array offers a scalable and viable alternative for DNA testing. The presence of DNA is translated into an electrical signal by biosensor for computer analysis. The distinctively and meticulously designed sensor chip has the ability to detect DNA efficiently. The novel vertical nanostructure design and two different surfaces of the sensor allow ultrasensitive detection of DNA [45]. Lab-on-a-chip (LOC) Lab Chip is a device which involves preparation of sample and detection of DNA array. The objective of this technology is to integrate multiple processes, including collection of sample and pretreatment of it with the DNA extraction, hybridization and detection, on single self-contained microchip i.e. on a microfluidic platform. The capability to do all the processes on a single chip merits excellent advantages in terms of cost, speed, efficacy, effectiveness, contamination, sample consumption and automation. Laboratory transportation to the source of sample will be enabled by such miniaturization of analytical instrumentation. The development of these credit-card sized microlaboratories is commonly based on latest micromachining and microfabrication technologies, utilizing processes well known in the manufacture of electronic circuitry [14]. Cell-omic sensors Cell based detection systems can be combined with the microarray probes generating the hybrid arrays of cells within arrays of DNA/protein probs. This allows multiparameters analysis [46]. Applications of DNA Biosensors Biosensors plays a distinguished role in the field of environmental quality, food analysis, study of biomolecules and their interactions, drug development, crime detection, medical diagnosis, quality control, industrial process control, detection system for biological warfare agents, manufacturing of pharmaceuticals and replacement organs. The applications of DNA biosensor can be classified into three broad categories: sequencing, mutation detection and matching detection [47]. Their main use is for diseases diagnosis. Numerous diseases can be diagnosed and variety of infectious agents can be detected using DNA biosensors. 1. Viral diseases By DNA microarrays Either viral detection were being carried by immunological techniques (i.e. use of enzyme-linked immunosorbent assays (ELISAs) for the detection of circulating virus-specific antibodies) or PCR based techniques (i.e. reverse transcriptase (RT) PCR is used to detect the presence of specific viral genes). Both these approaches possess some limitations. Immunological tests need specific antisera and the production of antisera is laborious and time-consuming task whereas PCR is prone to failure in its ability to identify multiple viruses simultaneously [48]. Therefore, recent advances in DNA and protein microarray methodology fulfill the need of a rapid and sensitive detection of viral infections (also identify multiple viruses in parallel). DNA microarrays for viral analysis can be divided into viral chips and host chips. Each not only detects and identifies but also monitor the viral populations. In 1999, the first viral DNA microarray for the temporal profiling of viral (human cytomegalovirus, HCMV) gene expression was described. Viral replication or de novo protein synthesis was blocked by treatment of infected cells with cycloheximide or ganciclovir and then the expression profiles of viral genes was generated using microarray. Using this approach, the HCMV genes were classified to immediate-early, early or late expression classes, on the basis of their expression profile in response to the drug treatments. This can be used as an identifying hybridization signature for the molecular staging of an infection [49]. Orthopoxvirus causes smallpox and has two subtypes variola major and variola minor, of differing pathogenicity. This problem of orthopoxvirus subtype discrimination was solved by producing an array capable of correctly identifying the four of the orthopoxvirus species by laassri etal. [50]. HIV genotyping was done using chip technology [51]. A unique signature that is derived from viral is provided by viral chips. Host chip is used for examining the host response i.e. changes in host gene expression. This provides a molecular signature of infection. Cummings and Relman exposed an idea of host chips [52]. Vant wout etal. examined HIV 1 infection in CD4+ T-cells to detect changes in host gene expression that were specific to HIV infection [53]. Proinflammatory genes and genes involved in endoplasmic reticulum stress pathways, cell cycle, and apoptosis were the host gene signatures identified. Detection of hepatitis B virus Hepatitis B virus (HBV) is one of the causative agents of viral hepatitis which is leading cause of liver cancer. Infection of HBV is a public health menace for worldwide resulting acute and chronic clinical consequences. Acute HBV infection may lead to liver failure or may progress to chronic liver disease. Some chronically infected individuals may subsequently suffer cirrhosis and liver failure or develop hepatocellular carcinoma. Effective antiviral therapy may inhibit or retard the progression to severe liver disease. By DNA optical biosensor Bacterial alkaline phosphatase (phoA) gene and hepatitis B virus (HBV) DNA were used as target DNA. For capturing the target gene onto streptavidin coated magnetic beads, a biotinylated DNA probe was used. A calf intestine alkaline phosphatase labeled DNA probe was used for subsequent enzymatic chemiluminescences detection. The detection cycle was less than 30 min, excluding the DNA hybridization time that was about 100 min. at fematomole or picogramme levels both phoA gene and HBV DNA could be detected. No response signal was obtained when in sample target DNA did not exist [54]. By Piezoelectric DNA biosensor HBV nucleic acid probe was immobilized onto the coated gold surface of quartz crystal using polyethyleneimine adhesion, glutaraldehyde cross-linking (PEI-Glu) method or the physical adsorption method. Better results were obtained with the coated crystal with the PEI Glu method to immobilized HBV nucleic acid probe than physical adsorption method with respect to sensitivity, reproducibility and stability. With the hybridization reaction, the mass is increasing that resulted change in oscillating frequency. The frequency shifts of hybridization have better linear relationship with the amount of HBV DNA, when the amount was in range of 0.02-0.14 microgram/ml [55]. By electrochemical DNA biosensor An electrochemical DNA biosensor that is a glassy carbon electrode (GCE) modified with label free21mer single-stranded (ss) oligonucleotides (related to hepatitis B virus sequence) via covalent immobilization. [Cu(dmp)(H2O)Cl2] (dmp = 2,9-dimethyl-1,10-phenanthroline) is used as an electrochemical indicator. The method is simple, economical and allows the accumulation of copper complex within the DNA layer. Cyclic voltammetry and differential pulse voltammetry were used for electrochemical detection. The detection of hybridization is accomplished by using [Cu(dmp)(H2O)Cl2], where electroactivity and strong association with the immobilized dsDNA segment lead to significantly enhanced voltammetric signal. The differential pulse voltammograms for the cathodic signals of [Cu(dmp)(H2O)Cl2] at a bare GCE, and at ss- and dsDNA-modified GCEs are also recorded. The peak currents of [Cu(dmp)(H2O)Cl2] increased in the order of bare GCE, ssDNA/GCE, and dsDNA/GCE. After hybridization process, a greater peak current was observed from dsDNA/GCE than at ssDNA/GCE, because that more [Cu(dmp)(H2O)Cl2] molecules are concentrated or bound to dsDNA helix than to ssDNA. Thus, [Cu(dmp)(H2O)Cl2] can be used as an electroactive indicator for recognition of the surface hybridization process. The sensitivity of the electrochemical hybridization assay was investigated by varying the target oligonucleotides concentration. The different current value obtained in the DPV response of [Cu(dmp)(H2O)Cl2] after hybridization of probe with target is recorded with three repetitive measurements. The current response at about 0.485V increased in proportion to the amount of the target sequence used [56]. Detection of hepatitis C 3a virus An electrochemical DNA biosensor i.e. a gold electrode modified with a monolayer of a peptide nucleic acid probe and 6-mercapto-1-hexanol was used that depends on covalent binding of the14-mer PNA probe (related to the HCV genotype 3a (pHCV3a) core/E1 region) onto the electrode. This self-assembled PNA could selectively hybridize with a complementary sequence in solution to give dsPNA-DNA on the surface, and this increases the peak current of methylene blue (MB) which is used for detecting target DNA sequence. Diagnostic performance of the biosensor is described and the detection limit was found to be 5.7  ÃƒÆ'-  10à ¢Ã‹â€ Ã¢â‚¬â„¢11  M with a relative standard deviation of 1.4% in phosphate buffer solution, pH 7.0. This sensor exhibits high reproducibility and could be used to detect the target DNA for seven times after the regeneration process [57]. Cystic fibrosis Mikkelsens team, pioneered the utilization of redox indicators, demonstrated utility of electrochemical DNA biosensor for detecting the cystic fibrosis F508 deletion sequence which is associated with 70% of cystic fibrosis patients. For the 4000-base DNA fragment, 1.8 fmol was the detection limit in relation to a Co(bpy)33+ indicator. High selectivity for the disease sequence (not for normal DNA) was accomplished by doing the hybridization at high (43 °C) temperature [14]. 3. Diabetes Diabetes is a worldwide public health problem. The diagnosis and management of diabetes requires a tight monitoring of blood glucose levels. Thus millions of diabetics test their blood glucose levels daily by making glucose the most commonly tested analyte. The challenge is to provide such reliable and tight glycemic control. Electrochemical biosensors for glucose thus play a leading role. Amperometric enzyme electrodes, based on glucose oxidase (GOx) bound to electrode transducers, have thus been found the subject of substantial research [58]. Glucose sensors are commonly used to measure the blood glucose level of diabetes patients. Using the latest DNA chip technology, many scientists at Diabetes Center have discovered the implication of new gene in the cause of type 2 diabetes. They created an abnormality in one of these genes known as ARNT (aryl hydrocarbon receptor nuclear translocator gene which is a member of a family of transcription factors) in mice and the mice developed changes in insulin secretion which were same as in patients with type 2 diabetes. The ARNT is required for the development of normal embryo. It is also related to responses to hypoxic stress condition and certain environmental toxins, such as dioxin and thus for integrating genetic and environmental insults it is present at specific potential sites. The expression of many other genes in the cell is regulated by transcription factors like ARNT and thus they are the master regulators of cellular functions. The first use of DNA chips has been represented by this study,

Woodrow Wilson

Woodrow Wilson was a politician, scholar, activist, and an idealist who believed that â€Å"there is no cause half so sacred as the cause of a people. There is no idea so uplifting as the idea of the service of humanity†. Yet he was also considered a racist. A. The Child Thomas Woodrow Wilson was born December 28, 1856 at Staunton, Virginia; one of four children to Joseph Ruggles Wilson and Janet Wilson who were of Scottish descent. His family moved to Augusta, Georgia a year after his birth and then in 1870 moving to Columbia and later moved to Wilmington in 1884. Woodrow later drop his first name, Thomas. B. The Student He got his early education from a few ex-Confederate soldiers who set up some schools after the Civil war and his father who taught him religion, literature and British history. At sixteen years of age, Wilson attended Davidson College, North Carolina for one year and later drop out of college due to his health. In 1875, he attended a College of New Jersey which is now known as Princeton University where he graduated in 1879. Later that year he studied law at the University of Virginia but left school again due to personal reasons. He continued his studying law on his own after returning home of Wilmington, North Carolina. He set up a legal practice with a friend from the University of Virginia in 1882 and passed the Georgia Bar Exam. Later, he left the practice of law and decided to continue his education at John Hopkins University, Baltimore. There he was enrolled as a graduate student in history and political science and earned his PH. D in 1886. With his research study, he made the dissertation known as Congressional Government: A Study in American Politics. In this dissertation, Wilson argued about the power the congressional government has over a weak postwar Presidency and for a constitutional change of separation of powers between Congress and the President to that of the British Parliament. In the final year of his graduate school, Wilson, at 28 years old, married Ellen Louise Axson, in Savannah, Georgia. They had three daughters in their life together, Margaret, Jessie, and Eleanor. Woodrow Wilson became an instructor at Bryn Mawr College from 1885 to 1888 teaching political economy and public law. He then accepted professorship at Wesleyan University in Connecticut, teaching history for two years. After 1890, he went back to Princeton University teaching political economy and law. From 1902 – 1910, Woodrow Wilson served as President of Princeton University. Wilson’s tenure helped shape Princeton into one of America’s great universities. C. The Governor Wilson ran for governor of New Jersey accepting the conservative Democrats’ proposal and won the democratic nomination. He shocked the politicians by declaring independence of the political bosses and later won the decisive victory over the Republican opponent and began his reforms against the political bosses. During two year period, Wilson had pushed legislation to allow voters to choose their candidates rather than having party bosses choose as well as secure reform for campaign finances. He also made passage for Workers Compensation for families whose working member is injured or killed on the job as well as improve the public utility commission to improve rates. During his time as Governor of New Jersey, many progressive leaders took interest in Wilson as a potential Presidential candidate, especially the Democrat William Jennings Bryan. D. The President Woodrow Wilson narrowly won the Democratic nomination in 1912 putting him against President Taft of the Republicans, Theodore Roosevelt of the Bull Moose Party, and Eugene Debs of the Socialist Party. Wilson on his platform presented a program called the â€Å"New Freedom† which busted up corporate monopolies to allow the chance for competition to prevent monopolies from controlling the Federal government. Wilson won the election with 41. 9% becoming the 28th President of the United States. Few reforms he first put out was the tariff reform, The Underwood Act; which had lowered rates from 40% to 27%, as well as creating the first federal income tax with the passage of the 16th Amendment. In 1914, Ellen Louise Axson, Wilson’s wife and First Lady, died from Bright’s disease. In 1915, Wilson married Edith Bolling Galt, who happens to be a widow at the time which made her the 2nd First Lady. With the Election of 1916 coming, the main focus came to light about the War in Europe, which Wilson being the Democratic candidate with Marshall as his running mate, bent on neutrality of keeping the United States out of the European War. His opponents were the reunited Republican Party with Charles Evan Hughes of New York as their candidate. Wilson called for military preparedness as well as a world association of peace for maintaining peace after the war in Europe ends, as well as women suffrage, and ending child labor. Democratic delegates also came up with the chant, â€Å"He kept us out of war† as the campaign slogan. Wilson had narrowly won the election in November with 49. 4% vote and 277 electoral vote compared to Hughes 46. 2% vote and 254 electoral vote. E. The Racist Wilson initiated his segregation efforts while president of Princeton University, he discouraged blacks from applying for admission. Wilson's History of the American People (1901) described the Ku Klux Klan of the late 1860s as a lawless reaction to a lawless period. Wilson wrote that the Klan â€Å"began to attempt by intimidation what they were not allowed to attempt by the ballot or by any ordered course of public action†. Wilson considered African American immigrants unfitting for American citizenship and unable to integrate in the American society. He made this very evident in his book, History of the American People. Wilson described slaves as â€Å"indolent† and compared them to â€Å"shiftless children† and thought that slave masters were patient with these lazy laborers. Woodrow Wilson disapproved of the idea of African American being free. He usual related them to animals and commonly referred to blacks as darkies. Wilson held the common neo-Confederate view that the South was demoralized by Northern advocates and Congressional hassle of black equality justified extreme measures to reassert white supremacist national and state governments. Though in 1912, â€Å"an extraordinary number of African Americans left the Republican Party to vote for Wilson (a Democrat), encouraged by his promises to support minorities, Wilson’s cabinet expanded racially segregationist policies. Under Woodrow Wilson administration, most federal government offices were segregated – in some departments for the first time since 1863. Many African American employees were demoted or fired. Some segregationist federal workplace policies introduced by the Wilson administration remained until the Truman Administration in the 1940s. In 1914, Wilson told The New York Times, â€Å"If the colored people made a mistake in voting for me, they ought to correct it†. F. The Public Administrator Wilson believed Public Administration was â€Å"government in action; it is the executive, the operative, the most visible side of government, and is of course as old as government itself†. He was fretful about the implementation of government so he studied public administration because he believed that it could increase governmental efficiency. He condemned political leader who modulated the importance of government administration and made it â€Å"†¦Ã¢â‚¬ ¦.. harder to run the constitution than to frame it†. Woodrow Wilson thought that the United States required greater compromise because of the diversity of public opinion. He compared administration to a machine that functions independent of the changing mood of its leaders. Wilson put it, â€Å"public attention must be easily directed, in each case of good or bad administration, to just the man deserving of praise or blame. There is no danger in power, if only it be not irresponsible. If it be divided, dealt out in share to many, it is obscured†¦. † II. Conclusion In 1919, Wilson suffered a stroke while on a speaking tour in Pueblo, Colorado, making him unable to carry out his Presidential duties effectively. After leaving office, he retired in Washington DC where he spent the remaining three years of his life before passing away on February 3, 1924. He is the only President to be buried in the National Cathedral in Washington DC. He changed the Democratic Party to a â€Å"party of reform† as well as changing foreign policy to internationalism from isolationism. He also left behind the Federal Reserve, the tariff reduction, federal regulation of business, as well as support for the labor unions. He helped prepare the United States for its role in the world with creating the League of Nations only for the US to join its; predecessor the United Nations. Woodrow Wilson left behind an idea that would fuel for global peace.

Being a Solomon Islander

I sit with my brothers and my cousins, watching our mothers stomp out the dance, their hips swaying and the dust kicked up by their bare feet settling in their hair. My mother seems to have been dancing for hours, her soft hair is covered in a fine layer of dirt, and her smile flashes every so often in my direction. The drums and pipes carry the light tone through the air and I clap with my brothers and cousins in beat with the motions of the dance, laughing and singing.Caught up in my own traditions, I can almost forget the voice of the missionary teacher who follows me each day as I join my older brothers in their daily journey to and from the waterside. I watch as they sail away from the shoreline, the long canoe gliding across the water. They can escape the confusing words of this colorless man who wears too many cloths and wonders still why he is hot. This man follows me and my friends as we trap lizards or play other boyish games, trying to dodge him and his talks of being burn ed in a volcano forever.My brothers tell me to ignore him, as they have. The missionary is not the threat, it is the kings who will take our homes and the food we eat. I hear my auntie telling my mother that morning as they prepared the pig for the feast later that evening, that the missionary plans to open a school and make me and my friends be students. My auntie told my mother, that my uncle feared they would teach us to be colorless too. For now though, we are away from the eyes of the missionary.My cousin says that he hides in his hut and prays for us to be thrown into a volcano when we dance. If only he could see my mother smiling and throwing her arms above her head. He does not look at us though, instead he follows and speaks of fire and his father, scaring my sisters and little brother. He scares me too but I will soon be a man, I am almost 9 already, I cannot show my fear. I will learn to laugh as my mother or walk away unhearing like my brothers and father.

How is the extinguishing of the Jewish and Native American...

I will be researching extinguishing of the Jewish and Native American races; the reasoning behind the atrocities, the suffering, and the aftermath. Both groups of people were stripped of their rights. The Native Americans were simply denied their rights and in Germany, during World War II, the Jewish population’s rights were taken away. The plight of the Native American expanded over a longer time period, but there race was practically eradicated. The systematic state-sponsored murder of six million Jews by Nazis and their collaborators took place during World War II, which was spanned a shorter timeframe. Two of the sources utilized throughout this essay, War and Genocide a Concise History of the Holocaust and Native American Genocide,†¦show more content†¦This was a contributing factor to the mass extinction of the Native American population. Most tribes lost anywhere from fifty to ninety percent of their people due to illnesses alone (Delema). On May 28, 1830, Andr ew Jackson enacted the Indian Removal Act; it was meant to encourage and assist [force] members of the five civilized tribes from eastern states to move west into the Indian Territory (Delema). Indian Removal policy was put into action to clear the land for white settlers. This act led to the Trail of Tears and more atrocities. The tribes decided to travel to the other side of the Mississippi. This commenced a relocation of over 70,000 Native Americans, a destructive movement known as the Trail of Tears (Delema). Many people died from exhaustion and starvation from the long journey. As America was expanding, Native Americans were being pushed farther west and even up into Canada (Delema). With Manifest Destiny and the United States constantly taking shape, the English settlers were much greedier for land and grew less tolerant of the Natives standing in their way. There were numerous amounts of massacres. There was a large migration to the west after the discovery of gold in Califor nia in1848 (Delema). The Homestead Act (1862) revived greed for money and land (Delema). In California and Texas there was blatant genocide of the natives by white men. â€Å"In California, the decrease from aboutShow MoreRelatedA Picatrix Miscellany52019 Words   |  209 Pagestheoretical passages, or to make certain doctrines seem less strange by administering them in small doses, or to demonstrate the equal validity of the magical and philosophical material, or for a combination of all three reasons. At all events, a similar method of presentation is apparent in one of the principal sources of The Aim of the Sage, the encyclopedia of the Brethren of Purity (Ihwà ¢n al-Safà ¢). What follows is a survey of the whole, with a sketch of the sources, as far as they can at present

Human Resource Management At An Organization - 1488 Words

As a human resource manager, there is a duty to manage workforce productivity. This adds on to the normal workload and responsibility of a human resource manager but is needed for optimizing the return on investment for the organizations’ labor expense. When looking at any organizations’ human resource department the main purpose is its effectiveness both in staff and in business. In order to be effective, most human resource managers first must develop an effective professional. That begins with the hiring process, great leadership and clear goals. High-performing employees are the foundation of productivity (Sullivan, 2011). To make a decent return on workforce investments, human resource managers must hire and retain employees, set direction and execute those directions. If the manager’s goals of the organization are clear and communicated the employees will be more motivated and focused because an unclear mission will result in a lack of focus and a low lev el of engagement and commitment toward achieving it (Sullivan, 2011). Two current trends in health care that are affecting human resources are technology and rising cost of healthcare. Technology is important to every industry however in the health care industry advancement mandates it. Every record that is collected, including that of the employees, have been transcribed into an electronic system. In correlation to that, most employees in the healthcare facilities must use some form of technology in their testingShow MoreRelatedHuman Resource Management : The Management Of An Organization1250 Words   |  5 PagesHuman resource management is the management of an organization to build and maintain the relation between the employee and the organization in order to meet business objectives and employee expectations. The process of hiring and developing employees so that they become more valuable to the organization. Human resource management is the governance of an organization s employee. HRM is sometimes referred to simply as human resource. HRM is the process of recruitment, selection of employee, providingRead MoreHuman Resource Management : The Management Of An Organization980 Words   |  4 PagesHuman Resource Management Overview Human Resource Management is the management of an organization’s employees. When a company designates a Human Resource (HR) department, those in HR are the ones responsible for overseeing the well-being of personnel in the workplace, and focus on how to attract, hire, train, motivate, and maintain employees of the organization. (DeCenzo, Robbins, Verhulst, 2013, p4). According to David S. Bright from the Raj Soin College of Business at Wright State UniversityRead MoreHuman Resource Management And An Organization Essay1140 Words   |  5 PagesHuman resource management is a tool in an organization, which focuses on the recruitment, management, and giving direction to the people who work in the organization. Human resource management is a vital component, which deals with issues concerned with people. Such issues include, hiring, performance management, developmental issues, safety, staff welfare, benefits and staff motivation. An organization cannot create a group of profess ional working staff without better human resources (Stewart, Read MoreHuman Resource Management : An Organization1420 Words   |  6 PagesHuman resource management is a term that is often used loosely and is assumed to be common sense, but the people behind good human resource teams know that those accusations are simply not true. HRM is all about how to manage people in the most effective manner in order to produce the best outcome for the company. HRM has many fascists, including recruitment of employees, initial training, hiring, advising employees, developing job descriptions, providing ongoing training to all employees, developingRead MoreHuman Resource Management : An Organization3527 Words   |  15 PagesHUMAN RESOURCE MANAGEMENT: Introduction: Human resource management is the all about of recruitment, employee’s selection, providing necessary training and skill development, assessment of employees, and all other factors related to the employees in organization. Human: refers to the skilled and unskilled workforce in the organization Resource: refers to limited availability of scarce Management: refers to the process of coordination of human resource in organization to get the best results is calledRead MoreHuman Resource Management : An Organization Essay1429 Words   |  6 PagesHuman resource Management is very important in every organization. It satisfies the needs of man power and creates an atmosphere where all employees can work together to achieve the goals of an organization. HRM role is to plan how to recruit right people and give experienced and well trained workforce to organization. It makes plans for training and development of human resource in an organization. The main functions of Human Resource Management in an organization are given below: 1. RecruitmentRead MoreHuman Resource Management : An Organization1524 Words   |  7 Pagestougher competition, Human Resource Management has taken on roles that have intermeshed them with the company as a strategic partner rather than just an individualized operating type system focused on simple tasks. Critical to a corporation’s growth and success is their ability to gain a competitive edge. Superior Human Resource Management assists the organizations fulfill its goals and attain success. This paper will outline why it is essential for Human Resource Management to transform beyond itsRead MoreHuman Resource Management : An Organization Essay1418 Words   |  6 PagesHuman Resource Management As competition increases around the world, leading companies in every business category have recognized that having a quality workforce can help the company gain a competitive advantage in the market. Many companies have started hiring people irrespective of their race, sex, religion, nationality etc. The critical thing for any company is to understand and use potential of their workforce. Building and managing top-quality workforce is not as easy as it may seem. In orderRead MoreHuman Resource Management : An Organization910 Words   |  4 PagesAccording to Greer, Youngblood, and Gray (1999), it appears that in today’s business environment, one might argue that human resource management (HR) departments are being questioned to change what is described as their bureaucratic culture and to be customer –oriented, and provide outstanding service. Thus, in order to accomplish this, one might argue that it requires outsourcing in combination with an internal HR focus on a particular organization’s core competencies, particularly when it meansRead MoreHuman Resource Management : An Organization Essay3485 Words   |  14 PagesAbstract Human resource management plays an intricate role to at every company. The human resource profession has grown rapidly throughout the years creating multiple departments which specialize in specific areas. Categorized as a large corporation, Nestle Purina Petcare Company utilizes all functions of HR management. Having an organized and developed HR team allows the company to function and develop efficiently. There are seven main functions in which human resource management can be categorized

A Review of The Use of Prayer and Scripture in...

A Review of: â€Å"The Use of Prayer and Scripture in Cognitive-Behavioral Therapy† Summary In Tan’s article, â€Å"The Use of Prayer and Scripture in Cognitive-Behavioral Therapy† published by the Journal of Psychology and Theology in 2007, he discusses integrating prayer and scripture with Cognitive Behavioral Therapy. Tan uses examples of integration from real-life counseling sessions that he has been involved in, as a counselor. Tan’s article first discusses the usefulness of CBT and other behavioral techniques in counseling (Tan, 2007). Tan discusses very early in his article that CBT is as effective as antidepressant medications and is more effective that cognitive therapy alone according to a recent placebo study (Tan, 2007). Tan states†¦show more content†¦Tan describes the seven steps used for healing prayer. The steps for healing prayer begin with a prayer for protections from evil, guided relaxation, and peaceful visualization. This is followed by painful visualization, prayer, patiently waiting for God’s intervention, and communion with God. At the end of the healing prayer, there is a closing prayer and then a debriefing. The use of scripture in the session can be useful in correcting misconceptions that clients may have about God’s will for them. Utilizing the scripture can better inform clients according to Tan (Tan, 2007). Scripture can also inform clients about areas of their life that need adjusting or are sinful. It can also help clients to adjust their thought processes and improve character (Tan, 2007). Tan goes on to state that utilizing these aspects of Christian CBT properly is beneficial for clients who have given informed consent. It is also beneficial for the counselor to become immersed in the discipline because it helps in the development of his or her own character as well (Tan, 2007). Reflection I was actually a little upset when the article ended because I had hoped that Tan would have been able to provide examples from more than one client. I was happy that Tan discussed the story of Jane who had, had such a profound spiritual experience. Tan states in the article that not everyone has an experience like that but everyone takes away some sense ofShow MoreRelatedUse of Prayer and Scripture in Cognitive-Behavior Therapy Essay638 Words   |  3 PagesReview of Journal Article â€Å"Use of Prayer and Scripture in Cognitive-Behavior Therapy† Review of Journal Article â€Å"Use of Prayer and Scripture in Cognitive-Behavior Therapy† Summary This article talks about Cognitive-Behavior therapy and using prayer and scripture appropriately, how to approach using biblical/ Christian values in therapy. The journal also talks about an historical overview of behavioral therapy, throughout the years. The commentary discusses the two component of mindfulnessRead MoreUse of Prayer and Scripture in Coginitiv- Behavioral Therapy1247 Words   |  5 PagesUse of Prayer and Scripture in Cognitive-Behavioral Therapy Integration of Psychology and Theology Tamala Rivers February 16, 2012 Summary This article focuses on the use of prayer and scripture in cognitive-behavioral therapy (CBT). First you must focus on the biblical approach which you acknowledge Gods love and deal with past hurts in a proper manner. You also must focus on Gods Holy Spirit and his scriptures. As the therapist you should not be in self, you have to focus on your clientRead MoreReview of Interventions That Apply Scripture in Psychotherapy1048 Words   |  5 PagesReview of Interventions That Apply Scripture in Psychotherapy Summary Garzon (2005) seeks to describe ways in which a therapist may use Scripture within psychotherapy interventions and to increase the awareness of therapists in these techniques. 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It will convey how this method of treatment will be assistingRead MorePsychology, Theology And Spirituality1267 Words   |  6 Pages A 4-MAT Review: Psychology, Theology and Spirituality in the Christian Counseling Introduction Mark McMinn is a trained psychologist who is known for his book that was written in 1996 called Psychology, Theology and Spirituality in Christian Counseling. McMinn had advocated for the Christians who are counselors for many years. McMinn is very experienced in the work and in his field of study. One of the biggest things that McMinn stresses is the importance of establishing and maintaining a goodRead MoreEvaluation Of A Psychiatric Treatment1610 Words   |  7 Pagesprovoked at school. Her psychotherapy sessions will consist of CBT (cognitive behavioral therapy) techniques and DBT (dialectical behavior therapy). 4.) I would refer her to an adolescent peer group counseling so she could be around other teenagers who are in treatment for suicidal ideation and bullying issues. I believe she would feel supported by a group setting as peer groups have shown that clients use and reinforce the therapy techniques learned in individual counseling towards the group counselingRead MoreAnxiety Disorder3897 Words   |  16 PagesFletcher, Student, Liberty University. Correspondence concerning this paper should be addressed to Jeffrey S. Fletcher, Jfletcher1@liberty.edu Abstract This research paper is designed to review articles and books of professional journals in anxiety disorders, definition of anxiety disorder, review of current and past treatments of anxiety disorders, the new section and changes to anxiety disorder in the DSM-5, new treatments for anxiety disorders and medications for anxiety disorders. ThisRead MoreThe Effects Of Effectual Daily Prayer On Mental Health5652 Words   |  23 PagesRunning Head: EFFECTS OF EFFECTUAL DAILY PRAYER 1 EFFECTS OF EFFECTUAL DAILY PRAYER 2 The Effects of Effectual Daily Prayer on Mental Health in Adults Diane T. Bethmann, RN, MSN Student Jennifer M. Wood, MSN, RN Chamberlain College of Nursing Author?s Note Diane T. Bethmann, MSN Student, Chamberlain College of Nursing Jennifer M. Wood, Department of Nursing Faculty, Chamberlain College of Nursing Read MoreSpirituality and Substance Abuse Recovery Essay2818 Words   |  12 PagesIntroduction According to the Center for Substance Abuse Treatment and the transtheoretical model of change, â€Å"for most people with substance abuse problems, recurrence of substance use is the rule not the exception† (Enhancing Motivation for Change, 1999, p. xvii). Relapse can and most likely will occur in recovery, and should be recognized as well as anticipated by substance abuse recovery counselors. 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Clinical Operational Management

Question: Describe about the Facts and terms for Clinical Operational Management . Answer: Introduction Operation management by virtue of its characteristics has become indispensable for an organization in modern generation health care service providing industry across the world. This also holds relevance in field of clinical practices required in health care sector (Yoder-Wise, 2014). This report is based on case study of St Angels Integrated Healthcare and therefore has followed a logical pattern with focus on identification of issues as per the given case study of the health care unit. Clinical operations depend on effective operation management and this report has highlighted some measures as form of recommendation for the health care unit so that prevalent situations can be controlled by the Clinical operational manager of the case study organisation (Langabeer Helton, 2015). One of the significant issues within any industry is the high rate of employee turnover. Within the sector of health care high staff turnover is a bane and cripples the efficiency significantly. Instances of high staff turnover have been observed in St Angels Integrated Healthcare. One of the main reasons for such high rate of turnover was inter-professional conflict. Again, communication and lack of scope of practice have been identified as other significant catalysts for such high rate of turnover. Surveys carried out for ascertaining this issue revealed certain bottlenecks and pertinent strategies for arresting such abysmal rate will also be discussed in the paper. As per the Press Ganey Satisfaction Surveys three key areas have been identified that require immediate attention. These are Professional Communication, Patient Information and Satisfaction with Service. Reports received from the patients indicated that different staffs and medical officers showed little concern and exhibited lackadaisical attitude while discharging medial duties. This has also caused negative media attention and holds the potential to blight the organisational image. Apart from such practices budget report and quality surveys have illustrated deviance from industry standards including highly sensitive areas of hand hygiene and patient injury. The report will also dwell on these factors and suggest effective recourses for overcoming such lacuna while delivering services to the intended audiences. Key issues identified The analysis of the case study sheds light on some important factors which are essential for the identification of issues the St Angels Integrated Healthcare confronts with. High rate of employee turnover is a significant issue for St Angels Integrated Healthcare because of constant change practices and high working load on staffs. This is a major concern for the case study organisation as the organisational vision could not be supported with higher employee turnover which could remarkably increase the overall business expenditure and could also reduce the profitability of the organisation as well. It could be observed from the provided statistical data that employee turnover in St Angels Integrated Healthcare has increased by thirty percent (Abdelhak et al 2014). Variance for employees is high and the unit is also over budget. The reputation of the health care unit has dipped and therefore recruitment of required number of international staffs is affected. Many nurses have unwilling ness to workwith the St Angels Hospital and the Surgical Same Day Unit as they think that their scope of nursing practice is very limited in the organisation and this though prompts them to leave their jobs and to seek for knowledge development by undertaking advanced roles in nursing (Bronzino, 2014). High discontentment among staff is noticeable from the case study of St Angels integrated health care and the rising dissatisfaction among staffs are due to high work pressure and frequent change initiated by the organization leaving the employees in confusion. Decrease in quality of the services could be improved with increase in scope of practices for the nurse staffs and more effective motivational strategies for the entire workforce (Reeves et al 2013). Some remarkable achievement by the health care unit is being awarded with Equal Opportunity in the Workplace Agency (EOWA) Award, decrease in water consumption across the facilities by five percent and many others. The organisation is affiliated With Australian Council on Healthcare Standards Organisation. However some areas of improvement are highly significant for the organisation to implement changes especially service delivery as well as pre services and post services quality require improvements (Bronzino, 2014). Thus some of the most significant improvement areas for the case study organisation are staffs and patient communications, better working scope for nurses and operational performance management for ensuring better quality in the daily service related functions for satisfaction of service users and so on. Service delivery cannot be complete without staff engagement and their elevated level of motivation (Abdelhak et al 2014). In the given case scenario, it is observed that there are some negative variances which are not indicators of effective operational management practice by the St Angel- surgical same day unit (Steed et al, 2011). Negative variances were in respect of management expenditure, medical and nursing expenditure, travel, staff education and pathology assessment as well as pharmaceutical expenses. Thus total negative variance is -340,400 due to difference in actual and budget expenses 1,548,400 and 1,208,000 respectively and this situation implies poor operational efficiency by the organisation (Reeves et al 2013). Lack of cost control initiative and cost control measures have generated this situation that have increased expenditures related to management, pharmaceutical, nursing and medical along with travel and training of staffs. The variance could be reduced with focus on implementing proper operation management and review of cost involvement and requirement of expenditures in the areas that increased the actual cost (Yoder-Wise, 2014). Again, one of the key issues as has been revealed by inspections and surveys was hand hygiene. Lack of compliance to this basic practice further complicated the issues within this particular entity. Reports of non adherence and disobedience have resulted in infection. Specific indicators of hand hygiene compliance were 82% for St Angels and 68% for Surgical Same Day unit. Such deviation from the established standard was in stark contrast to 6C's of nursing. In Australia, almost 10% of people admitted to hospital contracted Health Care Associated Infection (HCAI) costing the exchequer significant amount of money. Several barriers to hand hygiene are lack of awareness about hand hygiene, reluctance to frequently wash hands with soap due to concerns about dermatitis and even workloads. The Nursing and Midwifery Board of Australia stresses on the importance of hand hygiene and states that hand hygiene for nurses should be a daily practice. Alcohol based hand rub (AHR) has also been sugge sted as a viable alternative for individuals who have a tendency to develop dermatitis. Role of effective hand hygiene has also been eulogised by WHO and it was opined that such practices helped in preventing HCAI. One of the alarming trends as deciphered by quality report was the declining quality of treatment observed across a wide range of areas. Some of these areas include referral rates, cases of relapse post the surgery period, medication errors and patient injury rate. With the inception of the Surgical Same Day Unit the reputation of St. Angels was also bolstered. However the KPIs have been inconsistent of late with anomalies reported from areas like medication safety, falls and injuries and cases related to pressure injuries. Most of these issues can be tackled by adhering to the basic tenets of nursing and medication. Role of mentors have assumed a great role in providing quality care to patients and to demonstrate care, compassion and commitment while discharging duties. The six main areas include Hospital Acquired Complications, core, hospital-based outcome indicators, and patient safety reporting for hospitals, patient experience surveys in hospital and practice level indictors Dissatisfaction among patients has multiplied due to the factors like staffs dissatisfaction and lack of practice scopes for nurses as well. Lack of professional communication and consequent service deterioration has led to increasing patient complaints and discontentment. The poor operational performance of the organisation has resulted into over budget expenditures of the company which makes the situation even worse (Yoder-Wise, 2014). In terms of overall medication quality the picture is not by any means satisfactory. Units Acquired Infection Rate is above the national standards and also there is rise in number of patients returning to after surgery procedure and this pinpoints that medication and care practices by the organisation are erroneous (Gallan et al 2013). In the table given below the identified issues are presented with possible opportunities for improvement corresponding to each type of issues NUMBER ISSUES IMPROVEMENT OPPORTUNITIES 1 High employee turnover Encouragement of work among staffs by high level of motivation, reorganisation of work for reducing high work load, proper change management. 2 Lack of satisfaction among patients Collection of their feedbacks for reinforcing the weak areas of service and practices. 3 Over budget expenditures by the health care unit. Effective operational governance and cost control not at the cost of quality and services for patients or service users. 4 Lack of professional communication with patients Possibilities of improvement in current scenario by encouraging patient participation as well increase in communication with patients by providing them with timely feedbacks and answers to their queries, development of organisational communicational system depending latest technological facilities like ICT software. 5 Lack of scope of practices Assessment of current practices and focus on some domains for expansion of scope. The areas of practice could be medication management and associated process, ordering of investigations when deemed to be required as well as discharge management. 6 Improper quality controls by the organisation and quality variance compared to national norms. Quality to be focused on much adequately so that national benchmark could be complied with properly resulting into higher level of satisfaction among patients and profitability improvement. Improvement in medication and safety in medication could ensure reduction in errors in clinical practices. Implementation plan for development The given case scenario has originated the need of implementation of an appropriate development plan that would encompass several improvements in the aspects that required maximum focus by the management of the organisation. The implementation plan for development includes several strategies that could bring about overall improvement in the operational gamut in the St Angels Integrate health care. Low motivation among the staffs could be improved by planning for better motivational strategies for employees including better training, career growth opportunities, performance appraisal systems, good work environment, supportive leadership practices and many other strategic approaches. These will elevate the motivation among staffs (Steed et al, 2011). It is also vital to have nurse leadership in the organisation in this care setting. Work load can be properly allocated among the staffs by maintaining proper roster by considering some aspects like type of patients and acuity, staffs experience and number of patients, variation in shifting and available support to staffs. Implementation of digital database systems for managing daily work responsibility allocation operations for the staffs could be a greater help in that case (Yoder-Wise, 2014). Through nurse leadership, the care services and the medication could be much better as nurses can facilitate better care governance within the scope of policies and health care legislations. Nurse leadership can be effective for measuring risks for patients and also advocacy for patients and coordination at the time of care can be substantially enhanced (Hall, 2013). St Angels Hospital and the Surgical Same Day Unit need to implement clinical governance as a operational approach for ensuring higher level of service quality and care for patients. This needs to be worked as an integrated system for managing patient safety as well as to manage risks of decrease in quality (Nuti et al, 2010). At the same time the clinical workforce needs proper guidance in support of best available care options and technologies for improving care quality. It is has also become vital to review the skills of the managers, senior nurses and clinical professionals so that their abilities for providing better quality services to the patients and providing better guidance to the follower employees could be realised . Identification of care incid ents are required to be reported to the proper authority of the hospital and analysis of the incidents can be effective for improving safety systems by identifying the causes of the incidents. Budget variances need to be understood by finding out the causes of the variances (Abdelhak et al 2014). Special attention for cost reduction can be helpful for the hospital to control costs and decrease in variances between actual and budgeted. The hospital need to initiate talk with its suppliers if it is seen that cost is higher due to price increased by suppliers. Unrealistic and ambitious budget could increase negative variances and the hospital must ensure proper care while deciding projected expenditure (Reeves et al 2013). Benchmark to measure success Acquired infection rate in the hospital has increased beyond national standards and this requires the hospital staffs to follow hand hygiene and the standard in this respect is that eighty percent of the workers in the care setting need to follow 5 steps in hand hygiene. They must ensure that they cleanse their hands before they touch a patient, before cleaning or aseptic process, after body fluid exposure or risks, after touching a patient and surroundings of patients (Yoder-Wise, 2014). Current hand hygiene compliance is 82% by the St Angels hospital and 68 percent by Surgical Same Day Unit and this need to be improved more. Data as has been collected by an audit for Data Period One, 2016 contained reports gathered from 906 hospitals spread across the territory of Australia covering both the public and the private sector. The compliance rate was found to be 84 % with total moments being 647,349 and correct moments being 543,544. Thus it may be seen that St. Angels Hospital together with Surgical Same Day Unit are below the compliance level. The audit also revealed that compliance rate was highest after a procedure or Body Fluid Exposure Risk. When this rate is considered as a benchmark it may be observed that scope for improvement exists for St. Angels Hospital to develop hang hygiene compliance. Specific attenuation has to be given both before and after a procedure with greater care on Body Fluid Exposure Risk. (CQI) or Continuous quality improvement is effective benchmarking aspects that could be beneficial for the hospital to monitor and check quality issues (Lewis et al, 2014). For the hospital, local quality-collaborative acts as benchmark where in some performances encompass performance related data or knowledge and therefore the hospital could measure its performances and can try for ensuring improvement (Steed et al, 2011). Another basis of benchmarking is health related information technology vendor that allow evaluation in support their systems. Prevention and management of pressure injuries are also to be ensured by the hospital (Langabeer Helton, 2015). Standards for preventing falls and reduction in harm need to be complied with the hospital as the performance of the hospital is not satisfactory. National benchmarks are meant for making it obligatory for a health care unit to follow care practices for health benefits of patients. Also depending on the benchmarks, performance of the hospital can be evaluated by its management and large differences among actual performance and the standards could be minimized. This could be turned into significant level of improvement in the health care sector and the performance of the clinical operations as well as satisfaction among patients can be improved (Reeves et al 2013). Conclusion If the available scope of practices could increase level of contentment among staffs then, then as per the willingness of the nurses, medication management and process, discharge management and ordering of evaluation could be implemented but at the same time, the hospital need to have cost control mechanism for reducing costs for the purpose of reducing variance among actual and budget (Cardo et al, 2010). While implementing change the existing level of discontentment among staffs and low level of motivation could dissuade the change initiative by the hospital. Increase in motivation among the staffs could support the change initiative and change can be better managed (Reeves et al 2013). The case scenario given in the assignment reflects that St Angels Integrated health care has confronted several problems such as higher staff turnover, negative variances, drop in quality aspects, poor level of patient-staff coordination, and inadequate scope of practices for nurses leading to high attrition, lack of cost control mechanisms which are largely prevalent (Hall, 2013). Many nurses in the hospital were dissatisfied due to limited scope of practices and this has caused the hospital to suffer immensely in form of low level of care services for the patients or service users (Bronzino, 2014). The case scenario reflects some requirement of improvement by implementation plan including motivation strategies for staffs, consideration on enhancement of scope of practices for nurses, cost control mechanisms for controlling variances among actual and budget cost. Quality of medication and care for patients can be improved by comparing performance with benchmark performance in quality and service attribute for helping patients (Garland et al, 2010). This will improve the reputation of the hospital and the problem like difficulty in recruitment of skilled and talented staffs can be solved and the workforce can ensure better care in form of effective care services along with better medication and support to patients (Langabeer Helton, 2015). References: Bronzino, J. D. (Ed.). (2014).Management of medical technology: a primer for clinical engineers. Butterworth-Heinemann. Link https://www.abebooks.com/book-search/author/J-D-BRONZINO Cardo, D., Dennehy, P. H., Halverson, P., Fishman, N., Kohn, M., Murphy, C. L., Whitley, R. J. (2010).Moving toward elimination of healthcare-associated infections: a call to action.Infection Control Hospital Epidemiology,31(11), 1101-1105. Garland, A. F., Bickman, L., Chorpita, B. F. (2010). Change what? Identifying quality improvement targets by investigating usual mental health care.Administration and Policy in Mental Health and Mental Health Services Research,37(1-2), 15-26. Link https://www.people.vcu.edu/~masouthamger/mcleod-et-al-cpsp-special.pdf Lewis, S. L., Dirksen, S. R., Heitkemper, M. M., Bucher, L. (2014).Medical-surgical nursing: assessment and management of clinical problems, single volume.Elsevier Health Sciences. Link https://www.ctcpjournal.com/article/S1744-3881(15)30026-8/references Nuti, S., Vainieri, M., Bonini, A. (2010). Disinvestment for re-allocation: a process to identify priorities in healthcare.Health Policy,95(2), 137-143. Link https://onlinelibrary.wiley.com/doi/10.1002/hpm.2201/full Steed, C., Kelly, J. W., Blackhurst, D., Boeker, S., Diller, T., Alper, P., Larson, E. (2011). Hospital hand hygiene opportunities: where and when (HOW2)? The HOW2 Benchmark Study.American journal of infection control,39(1), 19-26. Link https://textlab.io/doc/570814/validation-of-the-how2-benchmark-study Langabeer II, J. R., Helton, J. (2015). Health care operations management. Jones Bartlett Publishers. Yoder-Wise, P. S. (2014). Leading and managing in nursing. Elsevier Health Sciences. Reeves, S., Perrier, L., Goldman, J., Freeth, D., Zwarenstein, M. (2013). Interprofessional education: effects on professional practice and healthcare outcomes (update). Cochrane Database Syst Rev, 3(3). Abdelhak, M., Grostick, S., Hanken, M. A. (2014). Health information: management of a strategic resource. Elsevier Health Sciences. Hall, R. (Ed.). (2013). Patient flow: reducing delay in healthcare delivery (Vol. 206). Springer Science Business Media. Gallan, A. S., Jarvis, C. B., Brown, S. W., Bitner, M. J. (2013). Customer positivity and participation in services: an empirical test in a health care context. Journal of the Academy of Marketing Science, 41(3), 338-356.