The equivalence margin is the largest difference that is clinically acceptable between the test (or experimental) drug and the active control (or reference) drug. This paper discusses the scientific principles, along with the regulatory issues, that need to be addressed when determining the equivalence margin for the biosimilar product. The concept of assay sensitivity is introduced, and the ways to ensure assay sensitivity in the equivalence trial are emphasized. A hypothetical example is presented to show how an equivalence margin is determined. The regulatory agency should carefully assess if the equivalence margin of the biosimilar product was determined using a scientifically valid and clinically relevant approach, not subject to selection bias. This is important because the consumer risk of erroneously declaring equivalence when in fact it is not must be controlled conservatively low in the approval of any biosimilar products.
Dietary Sucrose ; Selection Bias

Septoplasty is one of the most commonly performed operations in Otolaryngology. It is often considered an easy operation. Yet it is still accompanied by a relatively high rate of failure and complications. It is definitely not an operation in which one surgical technique can suffice for all circumstances. Rather it requires a variety of techniques in accordance to the various septal pathologies in order to achieve a favorable outcome. This study provides a comprehensive review of septoplasty including current concepts, historical background, classification, updated surgical techniques, and management of complications. In particular, the surgical techniques that ensure a successful correction and minimal complications are highlighted.
Dietary Sucrose ; Nasal Septum ; Otolaryngology

PURPOSE: The purpose of this study was to evaluate the effect of abutment material on screw-loosening before and after cyclic loading. Among the different materials of abutments, zirconia and metal abutment were used. MATERIAL AND METHODS:: Two types of implant systems: external butt joint (US II, Osstem Implant, Korea) and internal conical joint (GS II, Osstem Implant, Korea) were used. In each type, specimens were divided into two different kinds of abutments: zirconia and metal (n = 5). The implant was rigidly held in a special holding to device ensure fixation. Abutment was connected to 30 Ncm with digital torque gauge, and was retightened in 30 Ncm after 10 minutes. The initial removal torque values were measured. The same specimens were tightened in 30 Ncm again and held in the cycling loading simulator (Instron, USA) according to ISO/FPIS 1480. Cycling loading tests were performed at loads 10 to 250 N, for 1 million cycles, at 14 Hz, (by subjecting sinusoidal wave from 10 to 250 N at a frequency of 14 Hz for 1 million cycles,) and then postload removal torque values were evaluated. RESULTS: 1. In all samples, the removal values of abutment screw were lower than tightening torque values (30 Ncm), but the phenomenon of the screw loosening was not observed. 2. In both of the implant systems, initial and postload removal torque of zirconia abutment were significantly higher than those of metal abutment (P < .05). 3. In both of the implant systems, the difference in removal torque ratio between zirconia abutment and metal abutment was not significant (P > .05). 4. In metal abutments, the removal torque ratio of GS II system (internal conical joint system) was lower than that of US II system (external butt joint system) (P < .05). 5. In zirconia abutments, the difference in removal torque ratio between the two implant systems was not significant (P > .05). CONCLUSION: Zirconia abutment had a good screw joint stability in the condition of one million cycling loading.
Dietary Sucrose ; Joints ; Torque ; Zirconium

Necrotizing fasciitis is a rare, but life-threatening infection. Prompt diagnosis and early aggressive intervention is required for survival. However, there has been frequently occurred in delays of diagnosis and treatment due to its non-specific nature. Therefore, a high index of suspicion is needed to ensure timely intervention. We report a case of necrotizing fasciitis in a 7-day-old term healthy neonate.
Dietary Sucrose ; Fasciitis, Necrotizing ; Humans ; Infant, Newborn

In the UK, a person or organisation that creates risk is required to manage and control that risk so that it is reduced 'So Far As Is Reasonably Practicable' (SFAIRP). How the risk is managed is to be determined by those who create the risk. They have a duty to demonstrate that they have taken action to ensure all risk is reduced SFAIRP and must have documentary evidence, for example a risk assessment or safety case, to prove that they manage the risks their activities create. The UK Health and Safety Executive (HSE) does not tell organisations how to manage the risks they create but does inspect the quality of risk identification and management. This paper gives a brief overview of where responsibility for occupational health and safety lies in the UK, and how risk should be managed through risk assessment. The focus of the paper is three recent major UK incidents, all involving fatalities, and all of which were wholly avoidable if risks had been properly assessed and managed. The paper concludes with an analysis of the common failings of risk assessments and key actions for improvement.
Dietary Sucrose ; Humans ; Occupational Health ; Risk Assessment

In the UK, a person or organisation that creates risk is required to manage and control that risk so that it is reduced 'So Far As Is Reasonably Practicable' (SFAIRP). How the risk is managed is to be determined by those who create the risk. They have a duty to demonstrate that they have taken action to ensure all risk is reduced SFAIRP and must have documentary evidence, for example a risk assessment or safety case, to prove that they manage the risks their activities create. The UK Health and Safety Executive (HSE) does not tell organisations how to manage the risks they create but does inspect the quality of risk identification and management. This paper gives a brief overview of where responsibility for occupational health and safety lies in the UK, and how risk should be managed through risk assessment. The focus of the paper is three recent major UK incidents, all involving fatalities, and all of which were wholly avoidable if risks had been properly assessed and managed. The paper concludes with an analysis of the common failings of risk assessments and key actions for improvement.
Dietary Sucrose ; Humans ; Occupational Health ; Risk Assessment

During the last four years, the pyrosequencing-based 454 platform has rapidly displaced the traditional Sanger sequencing method due to its high throughput and cost effectiveness. Meanwhile, the Sanger sequencing methodology still provides the longest reads, and paired-end sequencing that is based on that chemistry offers an opportunity to ensure accurate assembly results. In this report, we describe an optimized approach for hybrid de novo genome assembly using pyrosequencing data and varying amounts of Sanger-type reads. 454 platformderived contigs can be used as single non-breakable virtual reads or converted to simpler contigs that consist of editable, overlapping pseudoreads. These modified contigs maintain their integrity at the first jumpstarting assembly stage and are edited by fragmenting and rejoining. Pre-existing assembly software then can be applied for mixed assembly with 454-derived data and Sanger reads. An effective method for identifying genomic differences between reference and sample sequences in whole-genome resequencing procedures also is suggested.
Chimera ; Cost-Benefit Analysis ; Dietary Sucrose ; Genome

OBJECTIVETo construct an acid-sensitive mutant of Streptococcus mutans (S. mutans) by transposon mutagenesis and to find a new gene related to the acid tolerance of S. mutans.

METHODSThe transposon Tn917 was delivered into S. mutans UA159 by the temperature-sensitive plasmid pTV1-OK bearing Tn917 and transposition of Tn917 was induced after incubation at non-permissive temperature (42 degrees C). Transposants harboring Tn917 in the chromosome were screened for the selection of mutant that had diminished growth at low pH. Southern analysis was performed with EcoRI (no cut within Tn917) digests of S. mutans UA159 and the selected aid-sensitive mutant, with DIG-labeled probe of 4.3 kb KpnI fragment of pTV1-OK containing Tn917. Genetic backcross experiment was performed by transforming the genome of the mutant to another S. mutans strain MT8148 to determine the linkage of Tn917 insertion to the change of phenotype (acid-sensitivity). Comparison of the abilities to grow at low pH, the glycolytic pH drop and killing pH values were done between the acid-sensitive mutant and the parent strain. The asymmetric PCR method was used to obtain the fragment flanking Tn917 and the PCR products were cloned to pMD18-T vector for sequencing.

RESULTSOne mutant that showed no growth at pH 5.0 was isolated from 2 316 transposants and was named as b23. Southern analysis and genetic backcross experiment confirmed the linkage between single Tn917 insertion into the chromosome and the phenotypic change (acid sensitive). b23 was less acid tolerant than UA159 in that it showed poorer growth at low pH and higher glycolytic pH minimum and higher killing pH. BLAST results indicated that Tn917 inserted into the genome of S. mutans UA159 at the site of 996 123 bp.

CONCLUSIONAn acid-sensitive mutant of S. mutans was successfully constructed and a new gene that is responsible for the acid tolerance in S. mutans UA159 was revealed.

No abstract available.
Animals ; Embryonic Structures* ; Freezing* ; Mice* ; Sucrose*

PURPOSE: We analyzed whether any problems existed in terms of the homogeneity of the Korean International Prostate Symptom Score (IPSS) questionnaire used in real practice. MATERIALS AND METHODS: Between July 2012 and August 2012, 48 Korean IPSS questionnaires used in real practice were collected. All the items on the questionnaire, including the quality of life (QoL) questions, were compared and we then determined the homogeneity of each question in comparison with the originally validated Korean version of the IPSS from 1996. RESULTS: Only 5 of 48 sources (10.4%) of the Korean IPSS totally corresponded with the original Korean version of the IPSS questionnaire. The consistency rate with the originally validated version was generally low for the answer choice items for each question, ranging from 16.6% for "less than half the time" to 35.4% for "almost always," with the exception of the item "not at all" (100.0%). The consistency rate was 60.4% for question 3 (intermittency) and 18.8% for question 6 (straining). No homogeneity was found in any of the QoL-related questions. The average consistency rate with the originally validated version was 42.2% and ranged from 22.9% for "unhappy" to the highest rate of 95.8% for "mostly satisfied." CONCLUSIONS: Compared with the originally validated Korean version of the IPSS, various Korean IPSS questionnaires used in real practice had significant problems in terms of homogeneity for both the questions and the answer choice items. Efforts are needed to ensure the uniform use of the validated Korean version of the IPSS questionnaire.
Dietary Sucrose ; Prostate ; Quality of Life ; Reproducibility of Results