Introduction Orthopaedic surgery consumes a considerable proportion of blood available to the National Health Service. Effective and judicious management of available blood is therefore vital. In order to review the usage of packed red cells in our centre, we carried out an audit involving patients who underwent total hip and knee replacement.Methods A retrospective audit was carried out to include all patients who underwent elective total hip and knee replacement, and underwent blood transfusion. A total of 449 patients were included and those who underwent transfusion were identified.Results Sixty five patients (14.5%) underwent blood transfusion. Approximately 5% required blood transfusion in both primary and revision TKR. 16% transfused in uncemented primary THR. 27.3% transfused in cemented primary THR. 30.7% transfused in uncemented revision THR. 77.7% transfused in cemented revision THR. 133 units were transfused in total out the 198 requested.Conclusion The present audit demonstrates that the cross matched to transfused ratio is within 2:1. Efforts should be made to reduce it to 1:1 where transfusion is necessary. This will aid in not only reducing the cost of transfusion, but also in reducing the risks associated with blood transfusion. INTRODUCTION Hip and knee joint replacements are very common and very successful orthopaedic procedures and the numbers done are increasing year on year. This is partly to do with the fact that it is being done in much younger age groups than before and due to the increase in the aging population. It is estimated that by 2033, 23% of the population will be aged 65 and above. Orthopaedic surgery consumes a considerable proportion of blood available to the National Health Service. It has been reported to be in the range of 10 – 15%. The increasing demand will further burden the National Blood service. Blood transfusion is accompanied by potentially fatal hazards. Although the risk of infection contracted through blood transfusion is declining, the non infectious serious hazards of transfusion will contribute to the morbidity and mortality associated with transfusion. It is also predicted that this might remain as a leading cause in the coming years. Effective and judicious management of available blood is therefore vital and should become part of joint replacement surgery. In order to review the usage of packed red cells in our centre, we carried out an audit involving patients undergoing elective total hip (THR) and total knee (TKR) joint replacement. The aim of the audit was to assess the extent of red cells being used and to compare it to other studies and also to serve as a baseline for future audits in our department. METHODS A retrospective audit was carried over a 6 month period between February 2008 and July 2008. A full list of patients who underwent elective THR and TKR was obtained. All patients who underwent blood transfusion were identified from the hospital transfusion register. Four hundred and forty nine patients were included in this audit. The trust guidelines for transfusion in surgical patients at the time of audit were that If pre op Haemoglobin (Hb) is less than 8g/dl & the surgery is associated with probability of significant blood loss (no time to raise Hb by other means) Pre op anaemia must be investigated Blood Transfusion In Hip And Knee Joint Replacement Surgery 2 of 4 Post –operative Hb falls below 8g/dl and the patient is distressed or actively bleeding RESULTS Out of 449 patients, 65(14.5%) underwent blood transfusion. One hundred and thirty three units were transfused in total out the 198 requested. According to the procedure, results are as follows. Figure 1 and 2 shows the units transfused and the percentage of blood used in total. Figure 1 Figure 1 No. of units transfused per procedure Figure 2 Figure 2 Percentage of blood used procedure wise Primary TKR using cement: Two hundred and seven patients underwent primary cemented TKR out of which 11 (5.3%) required transfusion. Ten patients were transfused 2 units and 1 patient was transfused 1 unit. 24/133 units were transfused in total (18.04%). Revision TKR using cement: Twenty four patients underwent revision cemented TKR out of which only 1 (4.3%) was transfused. 3/133 units were used (2.25%). Primary THR not using cement: One hundred and twelve patients underwent uncemented THR out of which 18 (16%) required transfusion. Three patients were transfused 1 unit, 13 patients were transfused 2 units and 2 patients were transfused 3 units. 35/133 units were transfused in total (26.31%). Primary THR using cement: Seventy one patients underwent primary cemented THR out of which 20 (27.3%) required transfusion. Three patients were transfused 1 unit and 17 patients were transfused 2 units. 37/133 units were transfused in total (27.81%). Revision THR not using cement: Twenty six patients underwent revision THR without cement out of which 8 (30.7%) required transfusion. Five patients required 2 units and 3 required 4 units. 22/133 units were transfused in total (16.54%). Revision THR using cement: Nine patients underwent revision cemented THR out of which 7 (77.7%) required transfusion. Two patients were transfused 1 unit and 5 required 2 units. 12/133 units were transfused in total (9.02%). Procedure wise, the cost per patient for transfusion was as follows: Primary TKR (11/207 pts) £16.19, revision TKR (1/24 pts) £18.22, primary un-cemented THR (18/112 pts) £43.66, primary cemented THR (20/71 pts) £70.81, revision un-cemented THR (8/26 pts) £118.22, revision cemented THR (7/9 pts) £186.29. Cost per patient group wise, was as follows: In total 231 patients underwent primary and revision TKR (207 and 24 respectively). The total cost of transfusion was £3,772.44. As a result, the cost per patient is £16.33. 218 patients underwent cemented & uncemented primary THR and cemented & uncemented revision THR (71, 112, 9 and 26 respectively). The total cost of transfusion was £14,810.32, giving the cost per patient of £67.93. DISCUSSION In a large study conducted in the US, the rate of blood transfusion in knee and hip replacements has been shown to be 39 and 57 percent respectively with an average of 46%. Others have reported between 37-90% for THR and for TKR it was found to be 22-97%. It was also noted that the average number of units transfused for THR and TKR was 2 and 1.6 units respectively. In another study, they compared the rates of transfusion in primary THR and TKR before and after introduction of a limited group and save policy. Their results showed a Blood Transfusion In Hip And Knee Joint Replacement Surgery 3 of 4 decrease from 32 to 28% in primary THR, and from 41 to 32% in primary TKR. Their crossmatched to transfused ratio (CT ratio) decreased from 3.5:1 to 2.3:1 and 1:1 after a re-audit. Similarly, the rates of transfusion for TKR was noted to be 58% and 35% , and that of THR was found to be 84% and 38% before and after implementation of the guidelines in another audit. The overall transfusion rate was also reduced from 71% to 37%. Repeat audit showed this rate was 32% (THR) and 48% (TKR) after a year. The average units transfused overall before and after guidelines was 2.3 and 2.4 units respectively. In our audit, the transfusion rate for both primary and revision cemented TKR was found to be approximately 5% which is well below other reported studies, and the transfusion rates for both primary and revision THR were comparable with the national average. (Uncemented THR 16%, cemented THR 27.3%, uncemented revision THR 30.7% and cemented revision THR 77.7%) The mean units transfused were 2.25 and 2 respectively for TKR and THR. Comparing their blood transfusion practice to national levels, Rogers and Johnstone found that CT ratio for THR fell from 3.21 to 1.62 for THR and 1.86 to 1.58 for TKR after implementation of guidelines and re-audit. In our audit, 198 units were requested out of which 133 were utilised. This is within the guidelines that recommend that the CT ratio should be 2:1. 11 The total cost of transfused blood given that the unit of blood cost 139.72 at the time of this audit, was £18582.76. Out of 196, 65 units were not utilised, and the cost of this is £9081.8. According to the British Committee for Standards in Haematology (BCSH) guidelines12, the primary goal should be to manage patients without the need for transfusion and avoid transfusion when haemoglobin is 10 g/dl. Numerous methods have been suggested and used to reduce the use of blood in elective THR and TKR. These include the intraoperative and perioperative cell salvage, antifibrinolytic agents, treatment of anemia, reviewing antiplatelet drugs and anticoagulation. Appropriate use of these could help with reducing the transfusion rate. CONCLUSION The present audit demonstrates that the CT ratio is within 2:1. Although this is within the recommended guidelines, efforts should be made to reduce it to 1:1 where transfusion is necessary. Individual units could audit their use of blood in THR and TKR. This would enable them to assess the extent of use and investigate any unnecessary wastage of blood and implement guidelines accordingly. This will aid in not only reducing the cost of transfusion but also in reducing the risks associated with blood transfusion.


From the earliest times, crowns have served as symbols of religious position and as signifiers of rank. Throughout the centuries and from culture to culture, crowns have varied in shape, material, usage and symbolism. CROWN JEWELLERY gives us an overwhelming overview including many photos of the actual crowns and regalia of the world. This publication highlights the evolution of crowns, different types and forms and their origins, and the precious materials used to make them. Royal events and ceremonies such as weddings, coronations and funerals are abundantly illustrated with extraordinary photos. In addition to royal ceremonies, the spiritual and religious ceremonies of ordinary life are also highlighted in this abundantly illustrated publication.


Mitochondria were deposited via dip coating on different substrates, namely, commercial glass, copper plate (Cu), aluminum plate (Al), and poly (methylmethacrylate). Mitochondria are organelles that are found in live cells. Mitochondria produce most of the ATP via oxidative phosphorylation. First, mitochondria were extracted for the thin film, as described in the literature. Capacitance properties of thin films were measured with Agilent LCR meter. SEM analysis was used for the surface analysis. The structure of mitochondrion was characterized with FTIR, whose spectrum was measured using a Perkin Elmer Spectrum 400 spectrometer. The stretching vibration of the P-O bond was observed at 1236 cm−1 in FTIR spectrum of the thin film. The capacitance and dielectric permittivity were first measured and calculated for the substrates, and then for mitochondria plated substrates. The properties, such as dielectric permittivity, capacitance, energy density, and power density of some substrates have been changed when...


Administrative law is increasingly faced with various challenges and growing social needs that require innovative solutions. The demands of social groups for greater efficiency of administrative law are expressed in the constitutional framework of the jurisdiction of the legislative, administrative and judicial authorities. At the same time, the legal nature of various types of administrative activities is being searched. Some of them are regulated for the first time by the new Law on General Administrative Procedure, thus becoming the subject of scientific and practical analysis. Persons carrying out administrative activities shall apply the standards of administrative procedures to which the insurance supervisory authority is also bound. The Law on Insurance, the Law on the National Bank of Serbia and regulations governing special administrative procedures regulate the legal position of the insurance industry and the National Bank of Serbia's supervisory and regulatory powers. The Insurance Law stipulates the Administrative Court cannot resolve an administrative matter in a dispute of full jurisdiction,


Poverty eradication or poverty alleviation is a set of measures both economic and humanitarian, that are intended to permanently lift people out of poverty. A field study was conducted on the socio-economic conditions of fishermen in Purulia District. The study was carried out for a period of 5 months with the objectives to know the socio-economic condition of involved fishermen and find out some possible suggestions to uplift the livelihood status of local fishermen. Socio-economic condition of tribal fishermen communities were presented in terms of, age group, religion, marital status, family type, condition of house, educational status of the fishermen, number of family members, school going children, school dropout children, household assets, use of electricity, occupation, sanitation, agricultural land, yearly income and expenditure, ownership of the domestic animals, source of drinking water, medical treatment, and loan etc. Fishermen villages are mostly located in inaccessible areas, where there is little communication and developmental or social impact. There is no denying the fact that fishermen and fishing community as a whole the poorest and most disadvantaged group of Purulia. They have no other activities except fishing, which cannot be carried out throughout the year and in idle periods, they lack alternative employment opportunities. Their socio-economic development is negligible. Hence it is essential to know the livelihood status of fishermen. Fishermen suffered many problems in this study area. So there is a necessary to manage and proper guideline for the proper use of resources by community people to ensure their livelihood pattern.


The Field Guide to Typography explores and explains the myriad typefaces that we see around us in our day-to-day lives, from airplane liveries to computer screens, from billboard hoardings to signage systems. It presents over 120 typefaces old and new, common and unusual with photographic references to help font spotters identify particular typefaces in the wild. Accompanying background information explains the origin, usage and key features of each typeface, and Field Facts provide little-known nuggets of information to expand your typographical awareness. Attractive and informative, The Field Guide to Typography is a unique visual reference for novice font fans and experienced designers alike, and a comprehensive celebration of our expanding typographic world.


Laser Surface Alloying of Chromium and Nickel on Iron and Carbon Steels ~. A. Molian, Ph.D. Oregon Graduate Center, 1982 Supervising Professor: William E. Wood The effects of rapid melting and subsequent quenching on the solidification behavior and solid state transformation structures of laser surface alloyed Fe-Cr, Fe-Ni, Fe-Cr-Ni and Fe-C-Cr systems were investigated as functions of composition (0-50%Cr, 0-20%Ni, 0-20%Cr/Ni, 0-1% C) and cooling rate (103_l06°C/s). The microstructures were characterized by optical, scanning and thin foil transmission electron microscopy. The effects of laser parameters (laser power, beam size and scan rate) and coating variables (composition, thickness and morphology) on the penetration depth and melt width were also evaluated. The microstructures of Fe-Cr alloys were ferritic in nature, irrespective of the composition (O-SO%Cr) and cooling rate (103_l06°C/s). The transformation structures of Fe-S%Ni and Fe-6%Cr-2%Ni alloys exhibited a mixture of martensite and ferrite. The transformation structures of Fe-C-Cr alloys were studied as functions of the carbon (0.2-l.0%C) and chromium contents (0-40%Cr). The alloys containing up to 10%Cr exhibited a martensitic structure with fine precipitates of M3C carbide and small amounts of retained austenite. The 20%Cr alloys consisted of duplex austenite/ferrite structures. The morphology and substructure of austenite were a function of the carbon content. Carbide precipitation


The increase in motor vehicle use is one of the important factors that cause traffic congestion, especially in megacities. Thus, the reasons behind this increase require serious attention. This paper offers an analysis of this kind, for a megacity from the developing world, Istanbul. A stratified multinomial logit model accounting for the availability of a second vehicle in the household is estimated for a sample drawn from a questionnaire to gather information of actual car use in Istanbul. This estimation is only possible through a unique data generation process that converts actual preferences into a choice study setting. In addition, a simulation study, generally utilized in the analyses of discrimination between certain layers of society, and a scenario analysis related to changes in income are also included in the paper for a better understanding of the nature of the topic. The results show that the behavior of households with a second vehicle available and not available varies significantly due to household, individual and professional-related characteristics.


In this paper we present a model of spatial competition that highlights firms' customization strategies in an imperfect competitive environment. The nature of competition in markets with products designed according to consumer preferences is discussed both in a framework of exogenous and endogenous set-up costs. Set-up costs are considered endogenous when technology is such that reductions in variable customization costs are feasible at additional set-up costs. It is shown that when set-up costs are exogenous, strategic interaction induces firms to choose the most efficient customization technology, though the latter entails a reduction in prices and profits and a more concentrated market structure. When set-up costs are endogenous, the incentive to choose strategically a more efficient customization technology depends on the possibility to cheaply transfer the customization costs into the set-up costs. This explains why customization is more frequently observed for information goods and in digital markets.


Vehicle powertrain electrification, i.e. combining the internal combustion engine (ICE) with an electric motor (EM), is a potential way of meeting the increased demands for efficient and low emission transportation, at a price of increased powertrain complexity since more degrees of freedom (DoF) have been introduced. Optimal control is used in a series of studies of how to best exploit the additional DoFs.In a diesel-electric powertrain the absence of a secondary energy storage and mechanical connection between the ICE and the wheels means that all electricity used by the EMs needs to be produced simultaneously by the ICE, whose rotational speed is a DoF. This in combination with the relatively slow dynamics of the turbocharger in the ICE puts high requirements on good transient control. In optimal control studies, accurate models with good extrapolation properties are needed. For this aim two nonlinear physics based models are developed and made available that fulfill these requirements, these are also smooth in the region of interest, to enable gradient based optimization techniques. Using optimal control and one of the developed models, the turbocharger dynamics are shown to have a strong impact on how to control the powertrain and neglecting these can lead to erroneous estimates both in the response of the powertrain as well as how the powertrain should be controlled. Also the objective, whether time or fuel is to be minimized, influences the engine speed-torque path to be used, even though it is shown that the time optimal solution is almost fuel optimal. To increase the freedom of the powertrain control, a small energy storage can be added to assist in the transients. This is shown to be especially useful to decrease the response time of the powertrain, but the manner it is used, depends on the time horizon of the optimal control problem.The resulting optimal control solutions are for certain cases oscillatory when stationary controls would have been expected. This is shown to be neither an artifact of the discretization used nor a result of the modeling assumptions used. Instead it is for the formulated problems actually optimal to use periodic control in certain stationary operating points. Measurements show that the pumping torque is different depending on whether the controls are periodic or constant despite the same average value. Whether this is beneficial or not depends on the operating point and control frequency, but can be predicted using optimal periodic control theory.In hybrid electric vehicles (HEV) the size of the energy storage reduces the impact of poor transient control, since the battery can compensate for the slower dynamics of the ICE. For HEVs the problem instead is how and when to use the battery to ensure good fuel economy. An adaptive map-based equivalent consumption minimization strategy controller using battery state of charge for feedback control is designed and tested in a real vehicle with good results, even when the controller is started with poor initial values. In a plug-in HEV (PHEV) the battery is even larger, enabling all-electric drive, making it it desirable to use the energy in the battery during the driving mission. A controller is designed and implemented for a PHEV Benchmark and is shown to perform well even for unknown driving cycles, requiring a minimum of future knowledge.


The aim of the studies described in the thesis was to study the functioning of patients with CIDP, MMN, or CIAP, and the determinants of their functioning. Specific research questions were: 1. What are the functional health profiles of patients with different inflammatory polyneuropathies (CIDP and MMN), and do these profiles reveal relevant determinants that can be studied further? 2. How can these determinants be assessed, i.e., what type of clinimetric instruments could be of value in these populations? 3. What are the functional health profiles of patients with CIAP and MMN established with these instruments? 4. What other determinant(s) might influence the functioning of patients with CIAP? The functional health profiles of patients with CIDP and MMN were investigated in a cross-sectional study on the basis of the International Classification of Functioning, Disability and Health (ICF) framework of the World Health Organization. The problems patients experienced in daily life were used to identify specific determinants of functioning and appropriate performance-based instruments. It was clear that dexterity and walking ability could be determinants of the functioning of patients with polyneuropathy. Because there are no specific instruments to assess dexterity and walking ability in these patients, the Sequential Occupational Dexterity Assessment (SODA) and the modified Shuttle Walk Test (SWT) were chosen as potentially relevant tests. The SODA has earlier been shown to be a valid tool to assess dexterity in patients with rheumatoid arthritis. Because the SWT was originally developed to assess functional capacity in patients with chronic airway obstruction and heart failure, the test was validated for the assessment of walking ability in patients with CIAP and MMN. Subsequently, the functional health profiles of patients with CIAP and MMN were assessed with the SODA and validated SWT, with help of the ICF. Functional health profiles differed between the patient groups. In addition to the functional health profiles derived from our studies, clinical experience has shown that pain might also be a determinant of the functioning of patients with CIAP. However, little is known about specific aspects of pain and its association with health-related quality of life. The pain patients experience was investigated in detail, using the generic McGill Pain Questionnaire. In summary, functional health profiles were established for patients with CIDP, MMN, and CIAP, and relevant determinants and performance-based instruments were selected. Functional health profiles differed between the patient groups. These findings indicated that it is essential to use performance-based tests in order to be able to assess problematic activities in detail. Effective methods to assess the pain experienced by patients with CIAP, and to assess balance in patients with CIDP and CIAP, are needed. The validated SWT proved to be of value in all patient groups, providing broad insight into patients' walking ability, and is a welcome new test for clinical use. However, the clinimetric properties of the SODA and SWT still have to be determined. Future studies have to be developed to tailor medical and rehabilitation therapy aimed at improving the functional health of patients with polyneuropathy.


A Public Key Infrastructure (PKI) is considered one of the most important techniques used to propagate trust in authentication over the Internet. This technology is based on a trust model defined by the original X.509 (1988) standard and is composed of three entities: the certification authority (CA), the certificate holder (or subject), and the Relying Party (RP). The CA plays the role of a trusted third party between the certificate holder and the RP. In many use cases, this trust model has worked successfully. However, we argue that the application of this model on the Internet implies that web users need to depend on almost anyone in the world in order to use PKI technology. Thus, we believe that the current TLS system is not fit for purpose and must be revisited as a whole. In response, the latest draft edition of X.509 has proposed a new trust model by adding new entity called the Trust Broker (TB). In this paper, we present an implementation approach that a Trust Broker could follow in order to give RPs trust information about a CA by assessing the quality of its issued certificates. This is related to the quality of the CA's policies and procedures and its commitment to them. Finally, we present our Trust Broker implementation that demonstrates how RPs can make informed decisions about certificate holders in the context of the global web, without requiring large processing resources themselves.


traditional numerical analysis. There is a short ALGOL summary, but the text consists mainly of some fifty "worked examples". For all but a handful of these both a flowchart and an ALGOL program are given. Although an excellent way of improving one's programming skill is to dissect good examples of the form, a genuine 'course book' should lead the reader into situations without always providing explicit solutions. This feature does however make it an excellent volume for the reference library shelf, or as support material for the mathematics teacher who wants numeric applications but who lacks confidence in his own programming ability. The second edition is virtually identical to the first for 200 pages, but is enlarged by the inclusion of two chapters which are presumably supposed to attract buyers who want a FORTRAN bias. No effort has been made to integrate this material into the rest of the book. A dreary example is chosen as a commercial application and the FORTRAN summary contains a number of oddities. Unlike the rest of the book, the layout of these two chapters is messy. It incorporates computer-produced output, some reduced in size, but most of which is disconcertingly large and 'furry', and has no advantage over the normal typeface. Another feature of my copy of the second edition is that the flowcharts (which were excellently crisp and well produced in the first edition) are often smudgy and occasionally unreadable. Also, someone has taken the trouble to incorporate some errors not present originally! These are heavy prices to pay for the replacement of the earlier 'sausage-shaped' decision boxes by the conventional diamonds. It is unfortunate that, in the revision, the authors did not seize the opportunity of including some interesting non-numeric examples using the extended string-handling facilities of many modern ALGOL implementations. This might have compensated for the book's rather outdated view of the computer as principally a mathematical tool for effortless 'number-crunching'. The discrepancy between the book's stated aims and its considerable achievements does not make it any less useful in this somewhat limited sphere, and every computing library should have one. I strongly recommend the first edition (secondhand copies if necessary) unless you happen to be a FORTRAN fetishist with good eyesight!


The relationship between pharyngeal infections, such as tonsillitis and pharyngitis, caused by group A beta-hemolytic streptococci (BHSA) and acute rheumatic fever (ARF) is a well-established fact confirmed by numerous studies carried out along the following lines: epidemiological, immunological, therapeutic, and prophylactic. The currently available data provide an opportunity to discuss the existence of «rheumatogenic» BHSA strains exhibiting a number of characteristic clinical and morphological properties. According to the current recommendations penicillins remain the means of first-line therapy for the treatment of acute forms of BHSA-induced tonsillitis and pharyngitis, whereas the macrolides should be applied only as the alternative medications in the patients with intolerance to beta-lactam antibiotics. This article contains characteristics of BHSA-carrier state and the principal indications for the prescription of antibiotics to the patients with these conditions. The key principle of secondary medicamental prophylaxis of acute respiratory infections are expounded along with the main lines of future research on the problems associated with BHSA-induced pharyngeal infections.


Summary

The effectiveness of ascorbic acid (AA), isoascorbic acid (IAA) and N-acetyl-cysteine (AC) in inhibiting browning of fresh-cut pineapple slices that were stored for up to 14 days at 10 °C, were studied. Slices treated with IAA and AA maintained higher levels of sugars and vitamin C than AC and controls. A low reduction of total phenolic content in treated slices was correlated with a lower polyphenol oxidase activity. IAA and AA slowed the degradation rates of sugars, vitamin C, and phenolic content, whereas AC was less effective in affecting these processes. A higher content of AA and IAA was associated with better compositional quality parameters and appearance of the pineapple slices during the storage period.


Worldwide, the prevalence of anterior open bite varies from (1% to 37.4%), the highest being in the French population whereas the lowest is in the Malta population. In the United States, the prevalence ranges between (16%) in black ethnicity and (4%) in whites. A similar study in Sudanese school children showed a much lower prevalence (1.1%). Open bites are multifactorial in etiology; they result from interactions between hereditary and environmental factors, and are divided into, dental open bite; without craniofacial malformations, and skeletal open bite involving craniofacial dysplasia. Skeletal open bite is characterized by a long anterior face height with the palatal plane tipped upward anteriorly, longer lower anterior face height, shorter upper anterior face height, and short posterior face height. The present study was designed to investigate these features as well as comparing them to Sudanese norms. This, hopefully, will assist in establishing a sound ground for orthodontists and maxillofacial surgeons to guide them to the proper diagnosis and treatment planning for anterior open bite.


Objective To investigate the efficacy of levonorgestrel-releasing intra-uterine system (LNG-IUS) treatment in patients affected by atypical complex hyperplasia/endometrial cancer (ACH/EC) wishing to preserve their fertility and to present fertility outcomes of those patients who actively tried to conceive. Methods Data of consecutive women with ACH/EC who underwent fertility-sparing treatment using LNG-IUS were retrospectively evaluated. Results Overall, 48 patients and the mean (±standard deviation) length of follow-up was 82.6±47.2 months. Among patients with ACH, 25/28 (89.3%) had a complete response (CR), 2/28 (7.1%) had a partial response (PR) and 1/28 (3.6%) had a progressive disease (PD). Mean (±standard deviation) time to CR was 6.7±4.0 months. Among patients with G1 EC, 13/16 (81.3%) had a CR, 1/16 (6.3%) had a PR and 2/16 (12.5%) had a PD. Mean (±standard deviation) time to CR was 5.0±2.9 months. Among patients with G2 EC, 3/4 (75.0%) had a CR and 1/4 (25.0%) had a PD. Mean (±standard deviation) time to CR was 4.0±0 months. Only 19 (39.6%) patients who had CR actually attempted to conceive. Eleven (57.9%) women tried to conceive naturally while 8 (42.1%) women underwent an in vitro fertilization (IVF). Fourteen (73.7%) patients wishing to conceive achieved a pregnancy (6 spontaneously and 8 through IVF). Conclusions Fertility-sparing treatment of patient with ACH/EC with LNG-IUS achieves high regression rates and good fertility outcomes. Future larger multi-institutional studies should be designed to confirm these preliminary findings.


We investigated the effect of BoNT/A injection on hip lateralisation in children with bilateral spastic cerebral palsy and bilateral adductor spasticity. Pelvic radiographs using Reimers' migration index (MI) were evaluated from 27 children (n=9 females, n=18 males; mean age 5.2 ± 1.96 years; range: 2-10 years; initial MI <50%) with bilateral spastic cerebral palsy over a time period of 2 years. All received injections of BoNT/A (Dysport) every 12 weeks with a dose of 30 Units per kilogram body weight into adductor and medial hamstring muscles on both sides. The MI was calculated before treatment and after 1 and 2 years. The mean MI increased from 25.5% (range: 0-48) to 26.7% (+1.2%, range: 0-79) on the right side and from 28.0% (range: 0-40) to 30.6% (+2.6%, range: 3-84) on the left side over 2 years, respectively. Hips of one patient dislocated bilaterally. The mean MI remained stable over 2 years. Although a specific BoNT/A effect cannot be proven because of the open design of this study, we provide strong evidence that the MI can be kept stable for a time period of 2 years under non-surgical management including therapy with BoNT/A even in CP patients with a high risk for hip dislocation.


Peanuts (Arachis hypogaea L.) are potentially a genetically vulnerable crop in the United States because of their narrow genetic base. To broaden the base, breeders must identify exotic parents for inclusion in programs of hybridization and selection. Parental, F1, and/or F2 performance could be used as indices to predict performance of inbred lines derived from crosses of adapted by exotic parents. Twenty-seven exotics representing five South American centers of diversity, Africa, and China were testcrossed to an adapted Virginia (ssp. hypogaea var. hypogaea) breeding line. The parents had been previously sorted into five morphological groups,. Parents, F1'S, and F2's were tested in 1979. Twenty F2 families per cross were bulked in the F4 and tested in 1981. Variation among bulks for pod and seed yield and other characters was due predominantly to differences among morphological groups. Exotics of ssp. hypogaea produced higher yielding bulks than those of ssp.fastigiata. Spanish (var. vulgaris Harz.) parents produced the hightest yielding fostigiata-derived bulks. Variation among bulks within morphological groups was significant for pod and seed size parameters and meat content, but not for yield. Performance of parents per se and F2's were the best indicators of F4 bulk performance, based on product moment and rank correlations. F1 performance, heterosis, inbreeding depression, and epistatic effects were largely unrelated to F4 performance. It was proposed that exotics' performance per se could be used as a criterion for selection of parents for yield, although inclusion of F2 yields in a multiple-variable index was more accurate in predicting F4 bulk means. Selection should be practiced within morphological groups of parents in order to retain parents from ssp. fastigiata


This study aimed to identify the health and functionality of the elderly with Type 2 Diabetes Mellitus in primary health care of Montes Claros-Minas Gerais, Brazil, featuring clinical and functional conditions related to daily life activities. Quantitative and descriptive research held in a Core area of support to family health, having as subject 99 elderly subjects with Diabetes Mellitus type 2. The data collection was conducted in the households of respondents, through structured questionnaire based on Functional assessment tools and the Brasilian Multidimensional Functional Assesment Questionaire. The data was analyzed by Statistical Package for the Social Sciences. In relation to clinical conditions, 94.9% have co-morbidities; 54.5% presented complications of diabetes; 84.8% reported feeling pain in at least one part of the body; 78% used some kind of prosthesis bracing; 26.3% and 22.2% reported hospitalization and fall last year, respectively. Referring to the conditions of functionality, 59.6% of the surveyed reported geriatric problems, with partial immobility mentioned 9.1%; 30.3% postural instability; 5.1% cognitive failure; 28.3% urinary incontinence and 23.3% presented difficulties in carrying out the activities of daily life. The degree of dependency, 79.8% presented dependency, being 40.4% mild; 20.2% moderate and 19.2%. severe, It is concluded that the extent of tieing-in of seniors surveyed was high, requiring of primary health care in charge of the construction and operationalization of appropriate health practices that reduce vulnerabilities and maintain and protect the health of the elderly against early aggravations of comorbidities generated by Diabetes


Two big bluestem (Andropogon gerardii Vitman) strains (Pawnee C3 and Kaw C3) developed by three breeding cycles for increased forage yield and in vitro dry matter digestibility (IVDMD) were compared with the base populations of 'Pawnee' and 'Kaw' in a 3-yr grazing trial. Pastures were seeded in May 1998 near Mead, NE. Experimental units were three 0.4-ha pastures of each strain or cultivar in a randomized complete block design. Pastures were burned and fertilized with ammonium nitrate at 112 kg N ha -1 in the spring of 2000, 2001, and 2002 before grazing. Each pasture was continuously stocked with three crossbred yearling steers (Bos taurus) (380 ± 38 kg) in mid-June 2000, 2001, and 2002 to provide a stock density of 7.5 steers ha -1 . Pawnee C3 and Kaw C3 produced 16 and 7% more average daily gain (ADG), respectively, than the base populations during the 3-yr study. Additionally, Pawnee C3 and Kaw C3 produced 14 and 5% more total body weight (BW) gain ha -1 , respectively, than the base populations. Pawnee C3 ADG was 1.30 kg hd -1 and produced greater than 455 kg total BW gain ha -1 during a drought period in eastern Nebraska. Pawnee C3 pastures produced more available forage with higher IVDMD, cell soluble, cell wall digestibility, and lower lignin concentration than forages from Pawnee pastures. Kaw C3 pastures differed from Kaw pastures by producing forage with greater crude protein concentration. These results demonstrate the productivity of big bluestem pastures in the eastern Great Plains and document the positive livestock response. to moderate increases in forage IVDMD. The strains bred for increased yield and IVDMD provided as much as 26% more total BW gain ha -1 at no additional cost. Pawnee C3 was released as the cultivar Bonanza and Kaw C3 was released as 'Goldmine'.


This paper examines how platform power is operationalized in the specific case of the iOS App Store. We take a first step in developing an analytical framework that critically examines the infrastructural power relations that constitute online platform ecosystems. Building on a relational understanding of power, we propose an analytical vocabulary to systematically interrogate the material power relations among the three main actors active in platform ecosystems: platform operators (e.g. Apple), third party institutions (e.g. app developers, businesses, governments), and end-users (i.e. individuals). To better differentiate among these three different actors in platform ecosystems, the paper proposes to study platform power at five expanding levels, similar to those of ecological ecosystems: individual actors, infrastructural platform services, company platform ecosystems, geopolitical platform ecosystems, and the global platform ecosystem. Studying infrastructural platform services, such as app stores, offers relevant insight into how globally operating platforms are able to set, steer, and bend rules and norms that impact individual actors on the local and national level. In the case of app stores, the paper shows that platform power is not casual or discursive, but highly strategic, uniform, and centralized. By interrogating the operationalization of platform power at the platform service level, the paper demonstrates that platform power is not a property of one platform itself, but a corollary of a platform's function in the context of other platforms and actors in a dynamic ecosystem.


A cornerstone of theoretical computer science is the Curry-Howard correspondence where formulas are types, proofs are programs, and proof normalization is computation. In this framework we introduce the atomic λμ-calculus, an interpretation of a classical deep inference proof system. It is based on two extensions of the λ-calculus, the λμcalculus and the atomic λ-calculus. The former interprets classical logic, featuring continuation-like constructs, while the latter interprets intuitionistic deep inference, featuring explicit sharing operators. The main property of the atomic λ-calculus is reduction on individual constructors, derived from atomicity in deep inference. We thus work on open deduction, a deep inference formalism, allowing composition with connectives and with derivations, and using the medial rule to obtain atomicity. One challenge is to find a suitable formulation for deriving a computational interpretation of classical natural deduction. A second design challenge leads us to work on a variant of the λμ-calculus, the ΛμS-calculus, adding streams and dropping names. We show that our calculus has preservation of strong normalization (PSN), confluence, fully-lazy sharing, and subject reduction in the typed case. There are two challenges with PSN. First, we need to show that sharing reductions strongly normalize, underlining that only β, μ-reductions create divergence. Our proof is new and follows a graphical approach to terms close to the idea of sharing. Second, infinite reductions of the atomic calculus can appear in weakenings, creating infinite atomic paths corresponding to finite ΛμS-paths. Our solution is to separate the proof into two parts, isolating the problem of sharing from that of weakening. We first translate into an intermediate weakening calculus, which unfolds shared terms while keeping weakened ones, and preserves infinite reductions. We then design a reduction strategy preventing infinite paths from falling into weakenings.


This research deals with assessment of geothermal potential in parts of middle Benue Trough, north-east of Nigeria. The study area lies within the Longitude 9°E – 10°E and Latitude 8°N – 9.50°N with an estimated total area of 18,150 km2. Regional/Residual separation was performed on the total magnetic intensity using polynomial fitting. The residual map was divided into 14 overlapping spectral blocks, and the log of spectral energies were plotted against frequency. Centroid depth and depth to top boundary obtained were used to estimate the Curie point depth isotherm, which was then used to compute geothermal heat flow of the study area. The result shows that the geothermal heat flow varies between 50.02 and 85.1 mWm-2 with highest value in the southern part (Akiri and Ibi) and north-western part (Pankshin) of the area. The geothermal heat flow obtained from this study indicates that the study area possess a good source of geothermal potential. The aero-radiometric data covering the study area was also analysed to estimate the radiometric heat contribution. The analysis of aero-radiometric data shows that the area possesses high content of Uranium, Potassium and Thorium. The radioactive heat production values vary between 1.58 μW/m3 and 2.53 μW/m3 with an average of 2.21 μW/m3. Thus, harnessing the geothermal potential in this area would be of added values and advantage to power generation in Nigeria.


JOHN S. HALDANE, M.D., LL.D., F.R.S., Late Reader in Physiology in the University of Oxford. CHARLES J. MARTIN, C.M.G., M.B., D.Sc, F.R.S., Professor of Experimental Pathology in the University of London Director of the Lister Institute, London. J. C. G. LEDINGHAM, C.M.G., M.B., D.Sc, F.R.S., Professor of Bacteriology in the University of London, Bacteriologist-in-Chief, Lister Institute, London. G. S. GRAHAM-SMITH, M.D., F.R.S., University Lecturer in Hygiene, Cambridge. MAJOR GREENWOOD, M.R.C.P., LOND., Medical Officer (Medical Statistics), Ministry of Health.


Retinoid signaling via retinoic acid (RA) and retinoid X receptors (RARs and RXRs) regulates mammary epithelial cell growth and differentiation. Loss of RAR-beta might represent an early event during breast carcinogenesis. Higher differentiated, estrogen-dependent, estrogen receptor (ER)-positive (ER+) mammary carcinoma cells have been found to contain relatively high levels of RAR-alpha and to be responsive to retinoids, whereas most undifferentiated, estrogen-independent, ER-negative (ER-) cells are characterized by low RAR-alpha expression and by retinoid resistance. In contrast, RAR-gamma is detectable at equal levels in both ER+ and ER- cells. In the present investigation, we directly examined the relative contribution of the distinct retinoid receptors to the retinoid response of breast cancer cells by comparing the effects of low concentrations of specific retinoids, which selectively activate individual receptor subtypes, on growth, cell cycle distribution, apoptosis, and on the autoregulation of RAR-alpha and RAR-gamma in ER- SK-BR-3 and ER+ T47D breast cancer cells. In vitro growth activity was determined by using a colorimetric cell viability assay and analysis of cell cycle distribution, and apoptosis was performed by flow cytometry of propidium iodide-stained or fluorescent Annexin V-labeled cells, respectively, whereas expression of RAR-alpha and RAR-gamma was determined by Northern blotting. Both cell lines are retinoid sensitive and express high amounts of RAR-alpha, RAR-gamma, and RXR-alpha. RAR-alpha-selective compounds (AM80 and AM580) inhibit cell growth, induce G1 arrest, stimulate apoptosis, and up-regulate RAR-alpha and RAR-gamma mRNA as efficiently as RAR/RXR-pan-reactive (9-cis RA) and RAR-pan-reactive retinoids (all-trans RA, TTNPB). Remarkably, an RAR-alpha antagonist (Ro 41-5253) not only blocks the RAR-alpha-selective agonists but also the pan-reactive compounds. In contrast, RAR-13-selective (CD417), RAR-gamma-selective (CD437/AHPN), and RXR-alpha-selective (Ro 25-7386) retinoids exert no effects on the examined parameters. Thus, our results support the idea that RAR-alpha is the crucial receptor mediating the biological effects during retinoid signaling in both ER- SK-BR-3 and ER+ T47D human breast cancer cells.


Jab1 is a co-activator of activating protein-1 (AP-1) transcription factor and the fifth subunit of the constitutive photomorphogenesis 9 (COP9) signalosome, which has been shown to mediate nuclear exportation and ubiquitin-dependent degradation of the tumor suppressor p27. Jab1 is overexpressed in several types of human cancer. However, de-regulation of Jab1 gene expression in cancer cells is largely unclear. In this study, we reported that expression of Jab1 was stimulated by HER-2/neu oncogene via transcriptional activation. Promoter deletion and mutation analysis indicated that HER-2/neu stimulated Jab1 via the T cell factor (TCF) binding site located at the K380/K368 region of the human Jab1 promoter. DNA affinity precipitation assay and chromatin immunoprecipitation assay verified that binding of b-catenin and TCF-4 to this consensus site was increased by HER-2/neu. In addition, dominant-negative mutant of TCF significantly attenuated the stimulatory effect of HER-2/neu. We also demonstrated that HER2/neu increased b-catenin/TCF-mediated Jab1 expression via the AKT signaling pathway because chemical inhibitor or dominant-negative mutant of AKT effectively attenuated the stimulatory action of HER-2/neu. IGF-I, which is a well-known AKT activator, also up-regulated the expression of Jab1 in NIH/3T3 and MCF-7 cells. Knockdown of Jab1 by small interfering RNA (siRNA) preferentially inhibited proliferation of HER-2/neu-overexpressing breast cancer cells. Taken together, our results suggest that HER-2/neu transcriptionally activates Jab1 expression to promote proliferation of breast cancer cells. Endocrine-Related Cancer (2007) 14 655–667


The internal physical mechanism of actual sound environment system is often difficult to recognize analytically from the bottom-up viewpoint, and it contains unknown structural characteristics. Furthermore, the observations in the sound environment often contain fuzziness due to several causes. In this paper, a method for estimating the specific signal for sound environment system with unknown structure and fuzzy observation is proposed by introducing a fuzzy theory and a system model of the conditional probability type. The effectiveness of the proposed theoretical method is confirmed by applying it to the actual problem of psychological evaluation for the sound environment.


Heat waves and droughts are a key risk to global crop production and quantifying the extent of this risk is essential for insurance assessment and disaster risk reduction. Here we estimate the cumulative production losses of six major commodity groups under both extreme heat and drought events, across 131 countries, over the time period of 1961-2014. Our results show substantial variation in national disaster risks that have hitherto gone unrecognised in regional and global average estimates. The most severe losses are represented by cereal losses in Angola (4.1%), Botswana (5.7%), USA (4.4%) and Australia (4.4%), oilcrop losses in Paraguay (5.5%), pulse losses in Angola (4.7%) and Nigeria (4.8%), and root and tuber losses in Thailand (3.2%). In monetary terms we estimate the global production loss over this period to be $237 billion US Dollars (2004-2006 baseline). The nations that incurred the largest financial hits were the USA ($116 billion), the former Soviet Union ($37 billion), India ($28 billion), China ($10.7 billion) and Australia ($8.5 billion USD). Our analysis closes an important gap in our understanding of the impacts of extreme weather events on global crop production and provides the basis for country relevant disaster risk reduction.


Adults with developmental disabilities have increased rates of mental illness and addiction, in addition to being more likely to experience physical health issues. This can lead to high rates of hospital and community-based healthcare. Population-based administrative health data can help in identifying the extent of problems experienced and target areas for policy and practice changes.


OBJECTIVES
Many studies have been carried out to investigate the individual effects of vitamin C, vitamin E, and ibuprofen on flap viability, with favorable results. This study aimed to determine the effect of combined use of these agents on flap viability.

DESIGN AND METHODS
Sixty Wistar rats weighing 250-300 grams were divided into six groups, equal in number, to receive saline solution (group 1, control), vitamin C (group 2), vitamin E (group 3), vitamin C and E (group 4), ibuprofen (group 5), and vitamin C, vitamin E, and ibuprofen (group 6). Following ketamine anesthesia, a caudally based reverse McFarlane flap on the back of the rats, 3x10 cm in size, was elevated and sutured back. The agents were administered intraperitoneally once daily for seven days, after which viable flap areas were estimated.

RESULTS
The percentages of the viable area of the flaps in groups 1, 2, 3, 4, 5, and 6 were 58.0%, 68.1%, 61.4%, 73.4%, 69.1%, and 80.5%, respectively. The use of vitamin C, vitamin E, and ibuprofen in combination resulted in a significantly greater flap viability compared to individual uses.

CONCLUSION
Administering vitamin E and vitamin C together has a greater effect on flap viability than used alone; however, the benefit is the greatest with the addition of ibuprofen.


The effect of the heat-treatment on the calcium phosphate deposited on Ti-6Al-4V substrate by an electrolytic process has been investigated. The calcium phosphate were deposited in a 0.04M Ca(H2PO4)2・H2O (MCPM) solution on Ti-6Al-4V substrate at 60 °C, 10V and 80 Torr for 1h, and calcined at different temperature for 4h. X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to characterized the deposited samples. The XRD pattern of as-deposited sample contain the phase of dicalcium phosphate (DCPD) and HAP. When calcined at 400 °C for 4 h, the DCPD phase is vanished and HAP becomes the major phase. The XRD pattern reveals that the intensity of HAP and Ca2P2O7 (CPP) decreases, but the β-TCP, CaO and rutile TiO2 also shows up.


Recent data concerning the effect of soybean 7S globulin subunits on the upregulation of LDL receptors in Hep G2 cells identified the alpha' subunit as the candidate responsible for this biological effect. In vivo evaluation of this subunit on cholesterol homeostasis was hampered by the lack of suitable amounts of alpha' chain. A novel separation procedure allowed us to investigate the effects of alpha' subunit administration on plasma cholesterol and triglyceride levels, as well as on the activity of liver beta-VLDL receptors of rats fed a hypercholesterolemic (HC) diet. Rats were divided into 9 groups fed the following diets for 28 d: standard diet; HC diet; HC diets + 5, 10, and 20 mg/(kg body weight. d) of alpha' subunit; HC diets + 50, 100, and 200 mg/(kg body weight. d) of soybean 7S globulin; HC diet + 200 mg/(kg body weight. d) clofibrate. The highest dose of the alpha' subunit decreased plasma cholesterol and triglycerides 36 and 34%, respectively, in rats fed the HC diet; 10-fold amounts clofibrate reduced plasma cholesterol and triglycerides 38 and 41%. The activity of liver beta-VLDL receptors of rats fed the HC diet with the highest dose of the alpha' subunit had a 96% increase in binding compared with the HC diet group, thus restoring the receptor activity to that of rats fed the standard diet. These results represent the first in vivo evidence of both the plasma lipid-lowering properties and the upregulation of liver beta-VLDL receptors induced by the soybean alpha' subunit.


A module M is called an absolute co-coclosed (absolute co-supplement) module if whenever M = T=X the submodule X of T is a coclosed (supplement) submodule of T . Rings for which all modules are absolute co-coclosed (absolute co-supplement) are precisely determined. We also investigate the rings whose (nitely generated) absolute co-supplement modules are projective. We show that a commutative domain R is a Dedekind domain if and only if every submodule of an absolute co-supplement R-module is absolute co-supplement. We also prove that the class Coclosed of all short exact sequences 0 /A /B /C /0 such that A is a coclosed submodule of B is a proper class and every extension of an absolute co-coclosed module by an absolute co-coclosed module is absolute co-coclosed.


Equine Assisted Activities and Therapy (EAA/T) is a non-invasive treatment modality recommended by the medical and educational community for a subset of challenged children and adults. As its popularity increases, so too are the concerns among stakeholders and the medical and educational professions about its legitimacy as a treatment modality. The main concern being that EAA/T practitioners have not acquired the professional skills required and that the EAA/T treatment programmes are not evidence-based. The central question of this research focused on identifying Equine Assisted Activities and or Therapy (EAA/T) and creating an optimal learning curricula and more practical experience for future practitioners. In order to explore these issues an extensive multi-method research study was conducted to identify gaps in EAA/T curricula, which included a review of empirical data and different curriculum models. The Delphi Method (DM), a robust, qualitative, naturalistic, systematic and interactive research method was used to support the research. Part of the DM required an analysis of data, adaptation of issues and amendments to questions culminating in a collective consensus among EAA/T experts. The key research findings suggested that current training programmes use curricula with significant gaps resulting in poor professional knowledge formation, a lack of experiential learning, insufficient knowledge of equestrianism and an inability to use pedagogic paradigms. Other findings showed that curricula being used were not being built as an application of sound theoretical principles but rather, transmitted in a manner that does not motivate active and meaningful learning or promote the best practical experience. As a consequence, national organisations and academies dedicated to EAA/T training sidestep high standards and core values for the sake of membership and financial gain. This rigorous research study has highlighted gaps in current training practices and has made it possible to make recommendations for a future curriculum. Recommendations that suggest the future curriculum is built on sound theoretical principles developing foundation knowledge to operate EAA/T in all fields of practice. This could set new quality and performance benchmarks and provides EAA/T practitioners with adequate tools to connect best practices to people with real-life challenges.


Abstract The European Convention of Human Rights system was originally created to sound the alarm if democracy was threatened in the member states. Yet, it eventually developed into a very different system with a focus on providing individual justice in an ever growing number of member states. This transformation has raised fundamental questions as to the level of difference and diversity allowed within the common European human rights space. Was the system to rest on minimum standards with room for domestic differences, or was it to create uniform standards? These questions have come up as increasingly contentious issues over the past years and have triggered a number of reforms seeking to introduce more subsidiarity in the system, striking a different balance between the European and national oversight of human rights. The article analyses this turn to subsidiarity by exploring whether the reform process has introduced new forms of difference and diversity within the common space of European human rights. Covering the period from 2000 to the end of 2019 and using a dataset of all judgments of the period, the article provides a structural analysis of developments in reference to the margin of appreciation which is the European Court of Human Rights' long-standing tool for balancing the common standards, yet leaving space for individual member states to find local solutions to implementing those standards. It concludes that recent developments have contributed to a more federal-style construction of European human rights with more space for differences within the common general standards.


Object-oriented application frameworks present one of the most successful approaches to developing reusable assets in industry, but developing frameworks is both difficult and expensive. Framework generally evolve to maturity through a number of iterations due to the incorporation of new requirements and better domain understanding. Since changes to frameworks have a large impact due to the effects on the applications build based on the asset, it is important to assess the maturity of a framework. Bansiya [3, 4] presents an approach to assessing framework maturity based on a set of design metrics and formulates four statements. In this paper, we present the results of a replicated case study of the framework maturity assessment approach. Our study subject consists of four successive versions of a proprietary black-box application framework. Our findings partly support the statements formulated in the original study, but differ in some places. The differences are discussed and explanations and argumentation provided.


ABSTRACT Introduction Mood symptoms are common features of Parkinson's disease (PD) and essential tremor (ET) and have been linked to worse cognition. The goals of the present study were to compare the severity of anxiety, apathy, and depressive symptoms in PD, ET, and healthy controls (HC) and to examine differential relationships between mood and cognition. Method Older adults with idiopathic PD (N = 448), ET (N = 128), or HC (N = 136) completed a multi-domain neuropsychological assessment consisting of memory, executive function, and attention/working memory domains. Participants also completed self-reported mood measures. Between-group differences in mood and cognition were assessed, and hierarchical regression models were conducted to examine relationships between mood and cognition in each group. Results Relative to the HC group, the PD and ET groups reported more mood symptoms and scored lower across all cognitive measures. There were no differences between the two movement disorder groups. Mood variables explained 3.9–13.7% of the total variance in cognitive domains, varying by disease group. For PD, apathy was the only unique predictor of executive function (β = −.114, p = .05), and trait anxiety was the only unique predictor of attention/working memory (β = −.188, p < .05). For ET, there were no unique predictors, though the overall models significantly predicted performance in the executive function and attention/working memory domains. Conclusions In a large cohort of ET and PD, we observed that the two groups had similar self-reported mood symptoms. Mood symptoms were differentially associated with cognition in PD versus ET. In PD, increased apathy was associated with worse executive function and higher trait anxiety predicted worse attention/working memory. For ET, there were no unique predictors, though the overall mood symptom severity was related to cognition. Our study highlights the importance of considering the relationship between mood and neuropsychological performance in individuals with movement disorders.


ABSTRACTYoghurt can be made from leguminose. In this research yogurt made from mungbean with addingl extract kelor leaves. This research is aim to know characteristic of mungbean yoghurt with adding extracts kelor leaves.  This research used Completely Randomized Design (CDR) factorial. First factor is starter consentratiton with three treatment level 5%, 10%, and 15%. The second factor is extracts kelor leaves consentration with two treatment 5% and  10%. Analysis was about total lactic acid, pH value, amount of Lactic Acid Bacteria, and viscosity. The best yoghurt will be analysis characteristic of sensory  ( quality of sensory and hedonic), proksimat (ash, protein, and fat content) and calcium. The best yoghurt is yoghurt with starter 5% and extract kelor leaves 5% contains 1,03% total lactic acid, pH value 4,54, total lactic acid bacteria 1,5 × 108cfu/g, viscocity 2200 cP, ash content 1,25%, protein content 5,58%, fat content 0,94%, and calcium 52,28 mg/100g.


If stream boundaries exist in flows simulated with molecular methods such as Direct Simulation Monte Carlo (DSMC), molecules inside the flow zone can leave the zone from these boundaries. At the same time some new molecules are introduced into the flow area through the stream boundaries. The number of new molecules and their velocities are calculated from the stream boundary conditions. Mostly two different methods are employed to perform stream boundary calculations. These are surface and volume generation reservoir methods. Each method has some advantages over the other. Two important disadvantages of the volume generation reservoir method are the lower number flux of the molecules compare with the theoretical number flux and lower computational efficiency compare to surface generation reservoir method. In this study it is shown that using a new approach to volume generation reservoir method, these disadvantages can be avoided.


In this article we examine exclusionary coalitions: groups of suppliers and customers that work collectively to keep out rivals and share in the resulting benefits. We offer a typology of horizontal and vertical coalitions, which we connect to economic theories about how exclusion is accomplished. Our exploration of these theories is embedded within an extended study of the Canadian sugar industry in the 1880s, which was controlled by an exclusionary coalition of refiners and wholesalers. Drawing upon this historical example, we assess several doctrinal approaches to establishing antitrust liability for anticompetitive exclusionary coalitions.


Despite the pronounced increase in feminist attacks on male supremacy during the second wave of the 1960s and 1970s, comparatively little has been written on feminist satire from this time. The following article examines two important essays from this era and illustrates the ways in which they take shape within the long tradition of satiric writing while critiquing that tradition in feminist terms. More narrowly, the essay suggests that the tonal and argumentative differences between the two texts can be attributed in part to their respective relationships to shifts in feminist theory between 1970 and 1973. Analysis of the two works reveals the close connection that existed in the 1970s between the writing of feminist satire and the development of feminist attitudes toward radicalism, the left, and anger in politics generally.


Aims. We present the spatial and diurnal variation of water outgassing on comet 67P/Churyumov-Gerasimenko using the (H2O)-O-16 rotational transition line at 556.936 GHz observed from Rosetta/MIRO in August 2014. Methods. The water line was analyzed with a non-LTE radiative transfer model and an optimal estimation method to retrieve the (H2O)-O-16 outgassing intensity, expansion velocity, and gas kinetic temperature. On August 7-9, 2014 and August 18-19, 2014, MIRO performed long steady nadir-pointing observations of the nucleus while it was rotating around its spin axis. The ground track of the MIRO beam during the observation was mostly on the northern hemisphere of comet 67P, covering its three distinct parts: the so-called head, body, and neck areas. Results. The MIRO spectral observation data show that the water-outgassing intensity varies by a factor of 30, from 0.1 x 1025 molecules s(-1) sr l to 3.0 x 10(25) molecules s(-1) sr, the terminal gas expansion velocity varies by 0.17 km s(-1) from 0.61 km s(-1) to 0.78 km s(-1), and the terminal gas temperature varies by 27 K from 47 K to 74 K. The retrieved coma parameters are co-registered with local environment variables such as the subsurface temperatures, measured in the MIRO continuum bands, the local solar time, illumination condition, and beam location on nucleus. The spatial variation of the outgassing activity is very noticeable, and the largest outgassing activity in August 2014 occurs near the neck region of the nucleus. The outgassing activity in the neck region is also found to be correlated with the local solar hour, which is related to the local illumination condition.


ABSTRACT: Field measurement of soil erosion is often desirable in soil conservation or management research. Conventional dyriamic methods (e.g., sediment and water collecting methods) are costly, laborious, and, in many cases, unavailable. This report from the tropical cropland in the Amazon region of Peru, describes a simple "mesh-bag" method for field assessment of soil erosion. A preliminay testing of nylon mesh-bags of 30 × 30 cm (12 × 12 in) with 5 mm (2 in) mesh on the top and 2 mm (.07 in.) mesh at the bottom were constructed and placed randomly in field plots and removed periodically to determine the quantity and quality of the eroded soil collected. Analysis of the variance indicated that the pooled coefficient of variation is seven percent within the side-by-side pairs; 24 percent within plots, and 42 percent within a management system. The efficiency of the bags stayed unchanged at least to the extent of 10 g (.35 oz) bag. Further testing of the method on 5 × 30 m (16.4 × 98.4 ft); 15–20 percent slope plots indicated that the amount of soil collected is independent of the position along the continuous slopes. The amount of soil collected in the bag correlated well with the product of rainfall × rainfall intensity (mm × mm/h). The mesh-bag method is reproducible and sensitive. By raking soil erosion under different practices in the field, it provides a simple means to sample eroded materials. Although the method is semi-quantitative at present. It has the potential to be developed into a truly quantitative method if rigorous evaluation under controlled environments and comparison with other conventional methods can be performed.


During the first year of NASA's Mars 2020 mission, Perseverance rover has investigated the dark crater floor unit of Jezero crater and four samples of this unit have been collected. The focus of this paper is to assess the potential of these samples to calibrate the crater‐based Martian chronology. We first review the previous estimation of crater‐based model age of this unit. Then, we investigate the impact crater density distribution across the floor unit. It reveals that the crater density is heterogeneous from areas which have been exposed to the bombardment during the last 3 Ga to areas very recently exposed to bombardment. It suggests a complex history of exposure to impact cratering. We also display evidence of several remnants of deposits on the top of the dark floor unit across Jezero below which the dark floor unit may have been buried. We propose the following scenario of burying/exhumation: the dark floor unit would have been initially buried below a unit that was a few tens of meters thick. This unit then gradually eroded away due to Aeolian processes from the northeast to the west, resulting in uneven exposure to impact bombardment over 3 Ga. A cratering model reproducing this scenario confirms the feasibility of this hypothesis. Due to the complexity of its exposure history, the Jezero dark crater floor unit will require additional detailed analysis to understand how the Mars 2020 mission samples of the crater floor can be used to inform the Martian cratering chronology.


: A new technique for the derivatization, the separation and the quantification of 2-acetylaminofluorene (2-AAF) and its metabolites biosynthetized by freshly isolated hepatocytes was developed combining gas chromatography and mass spectrometry. Analysis of the different metabolites was carried out after their derivatization into tertbutyldimethylsilyl compounds. Freshly isolated hepatocytes metabolized 2-AAF and produced five aryl-hydroxylated compounds as well as the N-hydroxy-2AAF and the 2-aminofluorene. The metabolites were found under their free and conjugated forms.


The barriers expressed by students during SAE development are beginning to follow a pattern. Traditional production-based SAE projects are not ideal for an increasing number of today's students, and the need for innovative, non-traditional projects is growing across the nation. Providing students with applicable, relevant experiences through which they can develop their agricultural knowledge is a critical component of an agricultural education program. Finding meaningful SAEs to address these barriers, as well as the changing practices of agriculture, can be daunting for even the most creative teacher. As agriculture becomes a more globally-intertwined industry, globally-focused SAEs offer opportunities for students to develop agricultural knowledge and experience in creative, easily-accessible ways. The theme of the March/April 2010 issue of The Agricultural Education Magazine was "An International View of Agricultural Education." In that issue, Dr. Boone, Editor, posited that an agriculture program does not have to center around one geographical perspective, although many currently focus on local agriculture (Boone, 2010). However, the need for and trend toward agricultural interdependence between countries creates an opportunity and a calling for students to become familiar with agriculture from a global perspective (National Research Council, 2009). Countries collaborate to maintain crop biodiversity (Hicks, 2010), test crop varieties in differing climates (Brasher, 2010), increase food security (Fayle, 20 1 0), and address global problems, such as climate change, water management, and hunger. The Consultative Group on International Agricultural Research (CGIAR) currently supports centers in over 100 countries whose focuses include forestry, livestock, food policy, crops, water management, fish, and tropical agriculture (CGIAR, 2010). Student connections to agriculture in other countries can begin with international agricultural organizations, such as CGIAR, The Food and Agriculture Organization of the United Nations, and the International Federation of Agricultural Producers. The presence of these organizations is an obvious sign that global agriculture is necessary and important; teachers are responsible for exposing students to the global trends in today's agricultural industries, and can do so through globally-focused SAEs. Traditional SAEs reflecting student interests are often not feasible due to a variety of student and situational factors. However, exposure to real-life situations involving these interests is still crucial to a student's understanding of agricultural practices. Blending student interests in agricultural practices with this international perspective helps turn traditional SAE projects into innovative, user-friendly SAEs that appeal to many of today's students (see Figure 1) Globally-based SAEs provide unique benefits to students, as well as to the entire agriculture department. By adding an international component to an SAE, the student gains an understanding and appreciation for factors that make up the world of agriculture existing beyond the scope of his or her previous personal experiences. Cultures that affect food selection and agricultural practices in foreign countries are typically out of the realm of student experiences, creating in these students a narrow view of what is "right" regarding what to eat and how food should be produced. Students exposed to cultural diversity in an exploratory, real-life fashion gives opportunity for a greater appreciation of the many cultural differences that dictate global agriculture industries. Many of the agricultural issues affecting communities are relevant problems in other parts of the world as well. Further, some of our nation's critical issues affecting policy, such as water management, the current unstable economy, animal welfare, alternative fuel sources, and environmental concerns, are shared with many nations due to their global nature. …


ABSTRACT According to Bernard Suits, people in Utopia would spend their time playing games and would not spend any time creating or engaging with artworks. Here, we argue against this claim. We do so by arguing that some games essentially involve aesthetic engagement with artworks. One type of game that seems to do so is dual-natured games, works that are both games and artworks. If utopians were to play such games, then they would be engaging with artworks. However, the possibility of dual-natured games has recently been called into question. With that in mind, we also offer a second kind of game that serves as a counterexample to Suits: art-inclusive games, which involve aesthetic and artistic engagement as part of their playing. After providing some examples of this kind of game, we show that the possibility of such games presents a problem for Suits' claim that utopians would not engage with artworks. If utopians were to play them, then they would be engaging with artworks. And as there is no good reason to think that utopians would not play such games, we conclude that Suits' claim about the lack of engagement with art in Utopia should be rejected.


The writer says aristol should not be used in the form of an ointment but should be applied directly to the wound. It is insoluble in water, but forms a tough brown pap with olive oil, which is, however, difficult of application. The undissolved powder itself is inert. Therefore, the ulcer should be strewn with powder, and a drop of olive oil be allowed to fall slowly from a glass rod upon it. Without waiting for the solution to be effected, the ulcer is promptly covered with some fine impermeable tissue, under which the solution takes place slowly. No cotton or charpie should be applied to the ulcer. If the secretions are very profuse, or if the ulcer is in an unfavorable location, this dressing must be secured by means of court plaster . The application should be renewed twice daily, after careful removal ofthat previously applied. Its advantages are that it is painless, odorless and non-irritating, and that there are no inconveniences attaching to its use. Painful ulcers become painless, and previously bedridden patients become able to go about after its use. If, however, as is the case in corroding or torpid ulcers, the healing tendency is not sufficiently rapid, recourse to iodoform must be had. Although aristol is not curative in soft chancres, nevertheless, where it is substituted for iodoform, there is no danger that the lesions will assume a more serious character. This happens frequently when mercurial ointments are used. In hard chancres its action is better. But it is of especial value in secondary lesions, in ulcerating gummata, in tubercular syphilides, etc. Although if continued long enough, this treatment will effect a cure, nevertheless it is hastened by the internal administration of anti-syphilitics. J Cutan Genito-Urin Dis. August 1892;10:332.


New techniques of capturing shape geometry for the purpose of studying asymmetry in biological objects bring the need to develop new methods of analyzing such data. In this paper we propose a method of mesh asymmetry analysis and decomposition intended for use in geometric morphometry. In geometric morphometry the individual bilateral asymmetry is captured by aligning a specimen with its mirror image and analyzing the difference. This involves the construction of a dense correspondence mapping between the meshes. We tested our algorithm on real data consisting of a sample of 102 human faces as well as on artificially altered meshes to successfully prove its validity. The resulting algorithm is an important methodological improvement which has a potential to be widely used in a wide variety of morphological studies.


Chronic kidney disease (CKD), and particularly kidney failure, is associated with accelerated atherosclerosis and approximately a 20-fold increased risk of cardiovascular death. The majority of these patients die from complications directly attributed to atherosclerosis and their life expectancy is decreased. Established risk factors are involved in the pathogenesis of this phenomenon. Age, gender, smoking, hypertension, dyslipidaemia and diabetes mellitus are among the established risk factors. Inflammation, qualitative lipid disorders (e.g. small dense low density lipoprotein), vascular calcification and oxidative stress represent emerging risk factors. The precise mechanism of atherosclerosis in patients with kidney failure is not yet known. CKD might represent a clinical model of atherogenesis. Thus, the evidence obtained from investigating "renal" atherogenesis could be of interest in improving our understanding of this disease process in the non-renal population. We review the relationship between "renal" and non-renal atherosclerosis focusing on pathogenesis, risk factors and clinical events and how they interact with treatment options. Overall, the "later" stages of CKD may eventually be considered as a coronary heart disease equivalent condition.


Hemp, eucalyptus, coal, hemp and coal blended fuel, and eucalyptus and coal blended fuel were ashed and then heat treated for 1 hour at temperatures from 600-1100°C. X-ray diffraction analysis indicated reactions between the phases present after initial ashing of the fuel showed biomass-biomass, biomass-coal and coal-coal interactions. Two phase systems were identified as dominant in the biomass and coal ash blends, these were CaO-MgO-SiO2 and CaO-Al2O3-SiO2. The phases identified in these systems have also been identified in ceramics produced at high temperatures which have similar compositions to the ash matrix of the laboratory synthesised ash; this indicates that phase diagrams can be powerful tools in phase formation prediction. Structures identified as trichomes (phosphate-silicate structures with melting points above 1100°C) from the hemp fuel which had not decomposed were present in both the hemp ash and the hemp and coal ash. The composition determined by Energy-dispersive X-ray spectroscopy analysis of laboratory synthesised ashes was also in agreement with the phases identified through X-ray diffraction.
Hemp and coal, eucalyptus and coal, and eucalyptus ash samples (deposited, quenched, cyclone, and bottom ash) removed from a full scale 1MWth combustion rig were analysed. Phase composition of the fly ash samples are similar to those identified in the analagous samples produced in the laboratory with several of the same phases present; confirming that laboratory testing is useful for the predictions of phases present on the industrial scale combustion rig. Particle morphology is one of the largest differences between the laboratory scale tests and combustion rig samples. The dominant particle shape of fly ash particles removed from the combustion rig is spherical. These particles of characteristic shape are often referred to as plerospheres and cenospheres and were first identified in coal fly ash. The presence of the spheres in the combustion rig when only biomass (eucalyptus) is present indicates the formation mechanism of the particles is similar to that of coal. There are similarities between the chemical composition of the spheres which are solely of biomass origin and co-fired; it is likely that phase composition of the sphere and not the fuel origin contributes to the formation of the spheres. Phases identified in the bottom ash are similar to those identified in the fly ash. High temperature phases such as (e.g. Ca9MgK(PO4)7) ocur in the bottom ash suggesting that higher temperatures are reached in the bottom of the rig than in the flue gas.
Analysis of 15Mo3 alloy corrosion coupons with fly ash deposited onto the surface, alongside the interactions between gas phases and coupons, deposits and coupons, and gas phases and deposits, showed that some oxidation/reduction of the metal had occurred. The presence
vi
of metal oxide flakes indicated corrosion. Oxidation of 15Mo3 alloy was observed in hemp and coal, and eucalyptus and coal combustion trials, likely due to the observed deposition of potassium chloride which has caused detachment of several scales. Between the metal-deposit interface, hematite whiskers were observed; magnetite octahedra were also present on the surface of scales. The phases present in the coupon deposit ash differ from those observed in the laboratory and fly ash due to the length of time spent in the high temperature environment. This indicates that some phases will not form until the deposits have built up and are in the furnace for an extended period of time. When the coupon samples were coated, fewer metal scales were observed meaning that the coatings are an affective method of corrosion reduction leading to an increased lifetime of boiler components.
The dominant particle morphology present in the combustion rig is the cenospheres and plerospheres. The phases formed can be broadly catergorised into CaO-MgO-SiO2, CaO-Al2O3-SiO2, and K2O-Al2O3-SiO2 phases. Potassium chloride is observed in the laboratory ash and combustion rig ash indicating, alongside the presence of metal oxide scales, that the fuel blends are likely to lead to corrosion during combustion.


In contrast to other discourse-centric explorations, I rethink the embodied experience of chronic pain through an affective ontology. Drawing on intensity, as a way of coming to know the qualitative experiential dimension of affect as diminished or heightened, I explore some of the complex relationships between intensity, desirability, and intentionality that cohere around pained bodies. In contrast to transient pain, chronic pain is presented as an undesirable affective intensity that has no recourse to intentionality and meaning but territorialises the body in ways that prevent other intensities from taking hold. Through an encounter with a pain-management programme, I explore a number of strategies for deterritorialising the chronically pained body in order to open it up to more desirable intensities. I argue that ultimately it is the progressive vulnerability and openness that deterritorialisation promises that is the key to becoming otherwise.


ABSTRACT Social attraction, that is, mimicking of active and productive colonies via audio playback of calls of breeding conspecifics and the use of decoys, is commonly used to attract birds to newly established or restored breeding sites. However, little is known about the relative importance of aural versus visual cues for identify nesting areas. Such information is important for design and evaluation of management protocols. We studied the effectiveness of decoys (visual cues) and playbacks (audio cues) as methods for restoring a colony of common terns (Sterna hirundo) at Muskeget Island, Massachusetts, USA. We used a 2-year, crossover experiment with 3 treatment areas: audio and visual, audio only, and visual only. We reversed treatment areas in the second year to control for previous nesting area or substrate preference. In both years, nests were built 9–101 m downwind of loudspeakers. There was no overlap in areas used for nesting between years and no nests were built within decoy plots in either year. Behavioral observations showed that birds responded to decoys only when within range of sound treatments. Conspecific vocalizations appear to be important proximate cues for seabird colony site selection and should be given priority in management protocols using social attraction.


Microplastics (MPs) are an emerging pollutant and a worldwide issue. A wide variety of MPs and tyre wear particles (TWPs) are entering and spreading in the environment. TWPs can reach waterbodies through runoff, where main contributing particulate matter comes from impervious areas. In this paper, TWPs and other types of MPs that were transported with the runoff of a high populated-impervious urban area were characterised. Briefly, MPs were sampled from sediments in a stormwater detention reservoir (SDR) used for flood control of a catchment area of ∼36 km2, of which 73% was impervious. The sampled SDR is located in São Paulo, the most populated city in South America. TWPs were the most common type of MPs in this SDR, accounting for 53% of the total MPs; followed by fragments (30%), fibres (9%), films (4%) and pellets (4%). In particular, MPs in the size range 0.1 mm-0.5 mm were mostly TWPs. Such a profile of MPs in the SDR is unlike what is reported in environmental compartments elsewhere. TWPs were found at levels of 2160 units/(kg sediment·km2 of impervious area) and 87.8 units/(kg sediment·km street length); MP and TWP loadings are introduced here for the first time. The annual flux of MPs and TWPs were 7.8 × 1011 and 4.1 × 1011 units/(km2·year), respectively, and TWP emissions varied from 43.3 to 205.5 kg/day. SDRs can be sites to intercept MP pollution in urban areas. This study suggests that future research on MP monitoring in urban areas and design should consider both imperviousness and street length as important factors to normalize TWP contribution to urban pollution.


BACKGROUND
A small number of studies have used different methodologies to measure primary non-compliance, but they have not established the reasons for patients not cashing their prescriptions. It has been suggested that the number of uncashed prescriptions is a measure of the quality of doctor-patient communication, but this hypothesis remains untested.

AIM
To establish the feasibility of obtaining data on a sensitive subject from patients by interview and to seek patients' reasons for not cashing prescriptions using qualitative data.

METHOD
Questionnaire administered to 1000 consecutive patients attending surgery, followed by interview with those patients who indicated that they had not cashed the index prescription.

RESULTS
The response rate was 93.5%. Twenty-two patients were included in the study. There was wide variation in the number of uncashed prescriptions issued by each doctor (1-13). A total of nine out of 22 patients reported that their medication was cheaper over the counter and obtained it in this way; 13 out of 22 did not obtain their medication. Five patients indicated that cost was a factor in not obtaining their medication. Other factors included the doctor's permission not to cash the prescription, poor understanding of the illness, and the wish to maintain control.

CONCLUSION
It is feasible to ask patients about aspects of their behaviour that may indicate, or cause, difficulties in the doctor-patient relationship. Prescribing behaviour varies widely between doctors and, although cost is a factor in determining whether a prescription will be cashed, other variables, such as the patient's desire to maintain control over the illness, may be more important.


More than 20 terrigenous sand beds, 1-9 m thick, were cored at 2 DSDP site in the lower Mississippi Fan, in 3300 m of water, 600 km from the shelf edge. The shallowest sand beds occur 15 and 23 m below the sea floor, and constitute 50% of the recovered cores. These beds were sampled at 20-30 cm intervals for size analysis. Sand content averages 80% with 10-15% variation within a bed. Mean and modal sand is fine grained and averages 2.75-3.0 phi. Maximum sand size ranges up to coarse sand, and within some beds, it varies between 0.5 and 2.0 phi. Grading is poorly developed on the scale of 1 m and larger. There is no consistent grading trend, and in some intervals, mean and maximum sand size show opposite trends. These data confirm that, like many ancient fans, the lower Mississippi Fan was a major site of sand deposition, but unlike them, consistent coarsening-upward sequences are not defined. The poorly developed grading, variations in grading trends, and changes in sand percentages result from sand deposition within a broad, shallow, meandering or braided channel in which sands are reworked. The many separate beds are probably the result of changesmore » in channel position that occurred on the average of once every 7000 yr. Sand transport to the lower fan ended at least 2000 yr before Holocene time. These newly discovered sand bodies, interlayered with finer clastic, potentially organic-rich material, suggest that stratigraphic reservoirs may be present in deep water, lower fan environments.« less


In middle-income countries, the informal sector often accounts for a substantial fraction of urban employment. We develop a general equilibrium model with matching frictions in the urban labour market, the possibility of self-employment in the informal sector, and scope for rural-urban migration. We investigate the effects of different types of growth on wages and the informal sector, and the extent to which labour market institutions can influence aggregate productivity. We quantify these effects by calibrating the model to data for Mexico, a country with a sizeable informal sector and significant labour market rigidities.


Colorectal cancer (CRC) is one of the most common cancer worldwide. However, a large number of genetic risk factors involved in CRC have not been understood. Copy number variations (CNVs) might partly contribute to the 'missing heritability' of CRC. An increased overall burden of CNV has been identified in several complex diseases, whereas the association between the overall CNV burden and CRC risk is largely unknown. We performed a genome-wide investigation of CNVs on genomic DNA from 384 familial CRC cases and 1285 healthy controls by the Affymetrix 6.0 array. An increase of overall CNV burden was observed in familial CRC patients compared with healthy controls, especially for CNVs larger than 50kb (case/control ratio = 1.66, P = 0.025). In addition, we discovered for the first time a novel structural variation at 12p12.3 and determined the breakpoints by strategic PCR and sequencing. This 12p12.3 structural variation was found in four of 2862 CRC cases but not in 6243 healthy controls (P = 0.0098). RERGL gene (RERG/RAS-like), the only gene influenced by the 12p12.3 structural variation, sharing most of the conserved regions with its close family member RERG tumor suppressor gene (RAS-like, estrogen-regulated, growth inhibitor), might be a novel CRC-related gene. In conclusion, this is the first study to reveal the contribution of the overall burden of CNVs to familial CRC risk and identify a novel rare structural variation at 12p12.3 containing RERGL gene to be associated with CRC.


With the availability of large amount of genomics studies, integrating information from multiple sources improves knowledge discovery. To address the complexity of genome and numerous genetic features, meta-analysis that aggregate information achieves higher statistical power for the measure of interest, and identify patterns among study results, sources of disagreement among those results.

As Next-Generation Sequencing (NGS) technologies are becoming affordable and can provide per-base resolution, NGS data serves as an appealing tool to analyze genomic fea-tures. Among various applications of NGS technologies, chromatin immunoprecipitation followed by high-throughput sequencing(ChIP-seq) is primarily used to provide quantitative, genome-wide mapping of target protein and DNA interaction events. Signal peak calling algorithms identified target regions of interest enriched in vitro. Despite the existing pro-grams for previous ChIP-Chip platforms, peak calling of putative protein binding sites from large, sequencing based data-sets presents a bioinformatic challenge that has required considerable computational innovation. Popular peak calling algorithms, such as MACS, SPP, CisGenome, SISSRs, USeq, and PeakSeq, are widely applied but each of them has different emphasis on sensitivity, specificity or different size and shape selection of peaks. In the first project of this dissertation, we propose a meta-analysis framework, ChIP-MetaCaller, to combine multiple top-performing algorithms to identify and reprioritize the peaks. We provide a forward selection algorithm to decide best combination of algorithms' output to perform meta-analysis and showed that the result improves motif enrichment and sensitivity. The results are more trackable by biologists for further validation and hypothesis generation.

The mechanisms of complex diseases like cancers involve changes in multiple genes, each conferring small and incremental risk that potentially converge in deregulated biological pathways, cellular functions and local circuit changes. To understand this complex network requires discovery of co-expression gene modules. Literature shows using meta-analysis can improve performance of identifying these modules from machine learning techniques in some pilot studies. In the second project of this dissertation, we proposed approach which is based on the clustering results of each individual study. Combining standardized distances from genes to the medoids lead to an integrated distance matrix and perform the meta-clustering. We compared the performance of proposed approach and Meta Clustering combining distance under three simulation settings and three real data sets and provide guidance for practitioners.

Two projects included in this dissertation tackles different biological questions based on genomics data. Both of them improve performance from existing methods by information integration applying meta-analysis frameworks, and provide comprehensive biomarker detection.This work could improve public health by providing more effective methodologies for biomarker detection in the integration of multiple genomic studies.


Essential hypertension is a clinical diagnosis based on the presence of an elevated systemic blood pressure on physical examination without a clear inciting cause. It has multiple etiologies and is not a homogeneous disorder. Hypertension contributes to the development and progression of atherosclerotic cardiovascular diseases, and antihypertensive treatment reduces the risk of fatal and nonfatal myocardial infarction, stroke, and congestive heart failure. Although hypertension is frequently present in nondiabetic individuals with low levels of proteinuria and chronic kidney disease, reducing blood pressures in this population does not reliably slow nephropathy progression. Many of these patients with recent African ancestry have the primary kidney disease "solidified glomerulosclerosis" that is strongly associated with renal-risk variants in the apolipoprotein L1 gene (APOL1). This kidney disease contributes to secondarily elevated blood pressures. The APOL1-associated spectrum of nondiabetic nephropathy also includes proteinuric kidney diseases, idiopathic focal segmental glomerulosclerosis, collapsing glomerulopathy, severe lupus nephritis, and sickle cell nephropathy. This article reviews relationships between mild to moderate essential hypertension and chronic kidney disease with a focus on the role of APOL1 in development of hypertension. Available evidence strongly supports that APOL1 renal-risk variants associate with glomerulosclerosis in African Americans, which then causes secondary hypertension, not with essential hypertension per se.