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(shylock, ‘the merchant of venice, act three scene one) in act three scene three, shylock swears that he will keep his promise of taking a pound of antonio’s flesh the poet wh auden wrote a poem ‘september 1 1939’ and in this poem there is a very famous line: “those who evil is done/do evil in return. Antisemitism in shakespeare’s the merchant one can’t escape it in the merchant of venice to shakespeare’s credit, shylock was a dynamic character who was. The merchant of venice, by william shakespeare in the merchant of venice shylock agrees to lend antonio three hundred ducats if antonio is willing. Shylock is the devil in the merchant of venice revenge and kill antonio in the merchant of venice, shylock was a person with william shakespeare. Or antonio/bassanio/shylock and antonio/bassanio/portia —shylock link between plots then portia takes over that role the merchant of venice by william shakespeare.
Shylock is the antithesis of their good and benevolent nature to conclude, however, that shylock is a villain is to miss the point of the merchant of venice while shakespeare's play depicts the jewish character as venal, the playwright does not ignore the context in which shylock acts. Free essay: shakespeare presents the character of shylock as a flesh eating, greedy and obsessive character in his play ‘merchant of venice’ by doing this. Although the plot turns on antonio's predicament, his character the merchant of venice william shakespeare and one of the reasons why shylock hates antonio. View full document the merchant of venice william shakespeare character list shylock - a jewish moneylender in venice angered by his mistreatment at the hands of venice’s christians, particularly antonio, shylock schemes to eke out his revenge by ruthlessly demanding as payment a pound of antonio’s flesh. William shakespeare wrote his play 'the merchant of venice,' in approximately the year 1600 shakespeare would have written this play to be performed at the globe theatre in london.
The merchant of venice and shylock’s character essay armish singh eng 245 a04 scott wilkins 02/14/13 shylock is a complex character from william shakespeare’s tragic comedy, the merchant of venice, who personifies jewish stereotypes and is despised and insulted by the other characters throughout the play. Shylock is a character in william shakespeare's play the merchant of venicea venetian jewish moneylender, shylock is the play's principal antagonist his defeat and conversion to christianity form the climax of the story. The merchant of venice is a 16th-century play by william shakespeare in which a merchant in venice must default on a large loan provided by an abused jewish moneylender it is believed to have been written between 1596 and 1599.
Shylock in william shakespeare's the merchant of venice essay - shylock in william shakespeare's the merchant of venice shakespeare has created a marvellous character in shylock he lives in veniceand he is a money lender. Merchant of venice study guide contains a biography of william shakespeare a friend of bassanio and antonio shylock merchant of venice characters. Antonio, a merchant of venice bassanio daughter to shylock magnificoes of venice william shakespeare the merchant of venice. Shylock is a character in william shakespeare's play the merchant of venice a venetian jewish moneylender, shylock is the play's principal antagonist his defeat and conversion to christianity forms the climax of the story.
Summary of william shakespeare's merchant of venice: shylock demands a pound of flesh that bassanio agreed to portia saves the day as a cross-dressing lawyer. The protagonist in the merchant of venice by william shakespeare is often considered to be antonio, as he is the character through whom all the other characters in the play are connected. Character analysis of shylock in “the merchant of venice” by william shakespeare posted by nicole smith, dec 7, 2011 poetry comments closed print in shakespeare’s edgy and suspenseful play, “the merchant of venice”, the character of shylock may evoke complex feelings within the reader. Shylock in william shakespeare's the merchant of venice essay shylock in william shakespeare's the merchant of venice the above statement suggests two assumptions firstly, that shylock is an unattractive character in the play i agree with this assumption, but only to a certain extent.
Antonio, shylock, bassanio, and portia are the main character in the merchant of venice antonio was a well respected businessman of venice he often loaned money out to help people but when his best friend bassanio asked to borrow money he could not helped him because his money was all tied up at that time. Villain or victim, shakespeare’s shylock is a take that scene in the merchant of venice in which shylock presses as for where shylock, should antonio. The merchant of venice by william shakespeare-character analysis/antonio/shylock/portia/bassanio-free book notes plot summary notes synopsis online study guide.
If the merchant of venice is one shakespeare's better known plays lacking a film shylock - al pacino antonio william shakespeare's the merchant of venice. Merchant of venice by william shakespeare same rights as the christian citizens of venice shylock is regarded as is taking an ounce of flesh from antonio. Antonio is a venetian merchant and the titular character in william shakespeare's the merchant of venice (first published in 1600, but known to. Shakespeare's shylock: character sketch shylock is one of the main characters in william shakespeare's the merchant of venice, a jewish antonio, shylock.
The duke of venice the prince of arragon and the prince of morocco, suitors to portia antonio, a merchant bassanio, his friend salanio, salarino, and gratiano, friends to antonio and bassanio lorenzo, in love with jessica shylock, a rich jew tubal, a jew, his friend launcelot gobbo, a clown, servant to shylock old gobbo, father to. This character analysis of 'the merchant of venice' reveals why shylock is one of shakespeare's best villains. The merchant of venice is a play by william shakespearethe title character is the merchant antonio, not the jewish moneylender shylock, who is the play’s most prominent and most famous character. The merchant of venice by william shakespeare home / the merchant of venice shylock there's no love lost between shylock and antonio shylock. An overview of antonio from the merchant of venice, from your trusted shakespeare source.


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This Matcha means jade foam . As for Gyokuru, three weeks before April pick, we have recovered the leaves with bamboo mats in order to concentrate the chlorophyll in the buds and the softest shoots. The leaves picked once a year a chopped, ..

domain: agronomy


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| Development cooperation
|| Church Work
|| Child sponsor program
Ethiopia is the oldest independent state in Africa and is around 3,000 years old. The country’s population is 81.2 million. Ethiopia is an extremely poor country: one quarter of the country’s population live on less than one US$ per day. Only one third of the population are literate. Life expectancy is about 50 years.
FELM’s partner organisation in Ethiopia is the Mekane Yesus Church. The Church is actively involved in health care and education provision, in addition to more traditional church work. The work of the Church has been praised by the Ethiopian authorities.
The Church’s income has not grown at the same rate as its membership and work commitments. FELM therefore supports the Church’s efforts to improve its financial management and become self-sufficient.
Food aid to drought areas
Certain areas in Ethiopia are in almost constant need of external food aid. FELM has supported the provision of emergency aid to Balen Gassera, as well as supporting a food security project that aims to promote self sufficiency and reduce the need for aid.
FELM and the Mekane Yesus Church provide various types of support to people in rural areas aimed at improving their quality of life. The local people have themselves identified their needs including: improved access to clean water through improving water management systems; training in health care for both people and animals; training in methods for increasing agricultural and livestock productivity; and support for the development of women’s livelihoods. The project has led to improvements in the quality of life of people living in the villages in question. For instance, villagers are now more healthy and have a more varied diet, the situation of women has been improved through providing them with entrepreneurial and vocational training and literacy classes have been organised.
Education for all is an important target for the Ethiopian government. FELM has supported various educational development projects in Ethiopia over several decades. The Mekane Yesus Church has done important work in improving the accessibility of education to children in remote areas and particularly in increasing girls’ school attendance.
A second important activity of the Mekane Yesus Church which FELM supports is developing education for deaf Ethiopians. The Hosaina School for the Deaf offers deaf children the chance to receive high quality education, which can be continued up to university level. The school has also developed a vocational training programme, which can help school leavers to enter working life. The children at the Hosaina School are supported through FELM’s child sponsorship programme. FELM has also supported the pioneering work of the Mekane Yesus Church in promoting the rights of the deaf, more widely, in Ethiopia. This work involves producing teaching materials, training teachers and working towards changing attitudes.
FELM also supports work to provide ethnic minority children from six ethnic groups with mother-tongue education. Mother-tongue education improves the educational results of ethnic minority children and strengthens their cultural identity. The work involves creating teaching materials and programmes in the languages in question and the training of teachers. FELM carries out this work in collaboration with SIL Ethiopia and the Ethiopian government.
HIV and AIDS work
The HIV and AIDS situation in Ethiopia has stabilized. It is estimated that there are 800,000 HIV-positive people and 1 million AIDS orphans in Ethiopia. The Mekane Yesus Church began its HIV and AIDS work in the 1980s and this work still constitutes an important part of the Church’s congregational and social activities. FELM has supported this work for around 20 years. The work includes prevention work, which consists of awareness raising and trying to change attitudes, as well as support to those who are living with HIV and AIDS. We have also provided support to children orphaned by AIDS in accessing education and finding work.
Healthcare is one of the basic services provided by the Mekane Yesus Church, which is supported by FELM. The modernization and new equipment that have been provided for the Atsaamo and Gemedo health centres have been important factors in reducing maternal and infant mortality and reducing incidences of malaria. Further training for health care professionals has improved the standard of care patients receive. As part of the development of healthcare village midwives have also been trained and awareness raising work carried out in remote areas concerning HIV and AIDS. Training on hygiene and nutrition are included in all community development projects.
FELM supports the proclamation work of the growing Mekane Yesus Church, as well as the training of its pastors and church workers in theological seminaries and Bible schools. FELM also supports the training of workers for women’s work, family work and diaconal work.

domain: sociology


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About Fate Margot Hayes Gray Wool Duffle Coat
The super gorgeous margot hayes coat is crafted with first-class wool material. For your whole comfort, we have interlined it with the lining of delicate viscose. The outfit comprises some really fascinating features like a toggle & buttoned style front closure, a wide turn-down collar, long-sewed sleeves, and chicest belted buttoned cuffs. Our about fate emma roberts duffle coat further entails two side flapped pockets and one internally attached pocket. It is available in the magnificent grey tone.

domain: design


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Sausages aren’t just unhealthy, but in fact, dangerous. Tejasvi Desai tells you why
You’ve probably been told to stay clear of sausages if you are watching your diet charts closely. But, did you know that apart from all the fat this juicy piece of meat has to offer, it also has carcinogenic properties that actually makes it dangerous for your consumption? If you’ve ever tried piling your hot dog up with spring onions and chopped tomatoes in hopes of making it healthier, condiments won’t really stand a chance against cancer.
The problem with sausages is that they aren’t only meat; it is a combination of ground meat mixed with fat, salt, a variety of seasonings, preservatives and sometimes other fillers. What makes the sausages really harmful are chemicals called nitrites and nitrates that are present in them, which once ingested can be converted into cancer causing compounds.
According to a spokesman for Cancer Research UK, these occur naturally in red meat but are often added during meat-processing as a preservative. Red meat also contains a red pigment called haems, which is broken down in the gut to form compounds that are known to cause cancer. Haems may even irritate or damage the cells lining the bowel, leading to a greater risk of developing cancer. The combination of these two, as well as the sausages’ relatively high fat and salt content make them some of the most dangerous foods we consume.
You might think buying better quality sausages with a high meat content could reduce the risk of cancer. But, sadly buying expensive sausages isn’t going to help much because high meat content means there will be less of other ingredients that could possibly reduce fat content such as cereals or fruits and vegetables that are often added to modern sausages for flavour. Instead of frying, grilled sausages will make a considerable difference to your cardiovascular health, but it won’t really diminish its carcinogenic properties. Some people try poking holes in them to let the fat run out, but what’s a sausage without fat?!
Cutting down on your consumption is the only healthy way out. If you still can’t control your cravings, then opt for a sausage with relatively low saturated fat and salt content. So, the next time you are about to pick up a hot dog, do think it over.

domain: food


Water heaters are something that we don’t necessarily think about until they stop working. They’re also a part of the plumbing world that has undergone several great changes throughout recent years. The old 20 to 50-gallon water heater that required at least 20 minutes to product lukewarm water has been replaced with a smaller, more efficient model that is completely tankless. Let’s take a look at the differences between large tank style water heaters and tankless water heaters.
The problem with big tanks is that they had to continually switch on and off to keep the water hot. The water within the storage tank cools down over time and must be reheated. Tankless water heaters, also called on-demand water heaters, heat the water as it is going through the pipes instead of in a holding tank. This makes them 27% to 50% more energy efficient than the big tank counterparts.
Water Heater Life Expectancy
The life expectancy of the traditional tank style water heater is roughly 10 to 15 years. Heating elements may need to be replaced at least once or twice during that timeframe. The life expectancy of a tankless water heater is more than 20 years.
The Initial Cost Factor
When on demand water heaters were introduced to the market they were at least twice as expensive as a tank model water heater. Today, however, they have come down in price and are very comparable to their much larger counterparts.
The Size Factor
On demand water heaters are much smaller than tank-style water heaters. Tanks require quite a bit of space and are generally stored under the home, in the basement, or in a closet away from view. Tankless units can be mounted near the shower or on the opposite side of the shower just to keep them out of view.
The Costs over Time
The average cost to operate a 50-gallon tank water heater is roughly $190 per year. The average yearly cost to operate a gas powered tankless water heater is roughly $170 per year. So we understand if you don’t want to base your decision on cost alone. A $20 difference per year isn’t going to make or break the bank at this point.
Never Run Out of Hot Water
This is the biggest advantage of a tankless water heater. You will never run out of hot water unless the unit malfunctions. A 50-gallon tank of hot water may last through four or five showers, but that fifth person may be rinsing off in cold water. Avoid finishing your shower in cold water by being the first to shower or purchasing and installing an on-demand tankless water heater.
We’ve been installing tankless water heaters for homeowners in the LA are for several years. The space saving design is what most Los Angeles area homeowners appreciate the most about these units. Give us a call at 310-644-9757 to discuss your options regarding tankless water heaters or to schedule a consultation.


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Resources and member news for Mary Robinette, John Scalzi, Sean Williams, Gail Dayton and Dan Wells!
Archive for the ‘News’ Category
SF Awards Watch reports that SFWA member Jedediah Berry has won the William L. Crawford Award. Congratulations!
The winners of the 2009 Aurealis Awards, honoring works of SF, fantasy, and horror by Australians, have been announced. Congratulations in particular, to SFWA members Ian McHugh, Jonathan Strahan, and Cat Sparks.
The Authors Guild is offering telephone seminars next week to help authors and agents who have questions about the Google Book Settlement. Remember the deadline to make a decision is January 28th.
On Jan 20, the American Society of Journalists and Authors (ASJA) , the National Writers Union (NWU), Science Fiction and Fantasy Writers of America (SFWA) and the Internet Society’s New York Chapter (ISOC-NY) jointly sponsored a workshop to discuss the implications for writers of the proposed Google Books Settlement (GBS). This is an audio of that panel.
Industry news and member news for Aimee Amodio!
Today, Science Fiction & Fantasy Writers of America, Inc., hosted an online panel discussion regarding the proposed settlement between Google, Inc. and the Authors Guild, Inc., and other class action plantiffs. The text-based panel ran for 90 minutes on the SFWA discussion forums, creating an instant transcript for writers who could not make the opening […]
Industry News and Member News for Catherynne Valente, Jess Wynne, Rick Boatwright!
Resources, Industry News, and Member News for Cate Gardner, Tracy S. Morris, Joanne Merriam, Jim Chines, John Scalzi, and Kim Mackey!

domain: literature


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|Mantri Greens in Malleshwaram||UP Haven in Seshadripuram||Nishitas Fortune Villa in Seshadripuram|
|Utham Nivas in Jai Bheema Nagar||Unishire Pratyaksh in Kumara Park||Shalimar Residency in Seshadripuram|
|Vaasthu Jayalakshmi in Seshadripuram||Nova Hamlet Krishnageet Apartments in Jai Bheema Nagar||SR Tamarind Tree in LB Shastri Nagar|
|Soundarya Devi in Sevashrama||Rakshitha Apartments in Jai Bheema Nagar||Ranka Nest in Rajaji Nagar|
|Rathna Mahaal in Jai Bheema Nagar||Shubham Apartment in Sampangirama Nagar||SM Fortune Paradise in Sampangirama Nagar|
|Asrithas Sheshadri Heights in Seshadripuram||Narayan Jahnavi Apartments in Seshadripuram||Renaissance Crags in Seshadripuram|
|VSPL Clover Enclave in Gandhi Nagar||Montreal Manor in Seshadripuram||Embassy KCN Mansion in Seshadripuram|
|Sai Venkateshwara in Seshadripuram||Hinal Heritage in Madhava Nagar||Rishab Apartments in Sampangirama Nagar|
|Moti Apartment in Seshadripuram||Jala Krupa in Seshadripuram||Perun Devi in Kumara Park|
In which area is Salarpuria Chamber located?The project is situated in Seshadripuram, Bangalore North.
Keep the question short and simple. Do not use SMS lingo. Use complete words. Avoid using any slang or abusive language.
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domain: geography


If you have a bad alternator and the vehicle battery gets low on voltage then the computer may not shift the transmission gears correctly and cause other drive symptoms like stalling or surges and rough shifts. Engine and transmission may even go into failure mode and cause various drive symptoms. Don’t worry the article discusses can a bad alternator cause transmission problems? Learn how to fix this problem?
Table of Contents
Can A Bad Alternator Cause Transmission Problems?
What Symptoms Does A Bad Alternator Cause?
- Dim or Overly Bright Lights
- Dead Battery
- Slow or Malfunctioning Accessories
- Trouble Starting or Frequent Stalling
- Growling or Whining Noises
- The smell of Burning Rubber or Wires
- Battery Warning Light on Dash
Can A Bad Alternator Cause Acceleration Problems?
The falls in the electrical power of a broken alternator can cause a malfunction of these systems, leading to a malfunction of the engine. Symptoms will be the slowing down, the failure, the poor acceleration, the hesitation and the stalling.
Will Your Car Start If Alternator Is Bad?
Cranking Troubles And Frequent Engine Stalls A failing alternator will have trouble charging the battery. In turn, the car battery won’t have enough power to start the vehicle. If the engine stalls almost immediately after a jump-start, then your car’s alternator is the likely root cause.
What Is The Average Life Of An Alternator?
“Its primary job is to keep the electrical system up and running in place of the battery. The battery’s job is to start the car, and the alternator keeps it running.” Gunning says an alternator typically lasts about seven years — or about 100,000 to 150,000 miles, says Waits.
Do Alternators Fail Suddenly?
The alternator is a key component in running the electrical systems in your car. When your alternator begins to fail it can cause a variety of different electrical problems in your car, and eventually cause a breakdown. Alternators can go bad suddenly, or slowly over time.
How To Fix A Bad Alternator?
Before You Start, Purchase The Right Kit For Your Alternator
The assumption is that you have already purchased a brush and regulator replacement kit for the model of alternator you have before starting this instructable.
Safety First, Disconnect The Car Battery
Disconnect the +ve from the battery for safety, I did not do this and bumped a +ve wire connected on the Alternator which created some brief fireworks, so my advice is to disconnect the +ve on the car battery first.
Remove The Alternator
Take some photos of the alternator in position and the orientation of the wire harness, ie the wiring socket at the rear of the alternator. Before unbolting the alternator ensure you unclip the wire harness on the rear of the alternator.
You may have to google for details depending on the make and model of your car. But typically two bolts hold the alternator in place, one long pin bolt on the underside of the alternator and a short bolt through a slotted bracket on the top of the alternator. Unbolt both, the long pin bolt might take a little effort to remove, but with patience and persistence, you’ll get there.
Remove The Rear Cover On The Alternator
Now you have removed the alternator, remove the plastic cover on the rear of the alternator, typically there are two bolts to be removed to remove the cover.
Remove Old Regulator And Brushes, Fit New Kit
With the rear cover on the alternator removed, take some photos of the regulator, and wiring to and from the regulator and the brushes. These may be handy should you have issues refitting the wiring.
Now remove the old brushes and the old regular ones. When removing the brushes check the length of the old against the new to see how much the old have worn.
Install the new regulator, and note wiring instructions from the supplier with the upgrade/repair kit. Install new brushes, reconnect wiring and refit bolts, and tighten (be mindful not to over tighten as the bolts are probably screwing into brittle plastic). Double-check wiring against your previous photos and the instructions that came with the kit.
Refit Black Plastic Cover
Refit the Black plastic cover to the rear of the alternator.
Refit The Alternator
Refit the alternator back into your vehicle and make sure the fan belt is tight.
Now Run Some Tests To See If You Have Fixed It
Attach your multi-meter +ve to car battery +ve and multi-meter –ve to car battery –ve, and set the multi-meter voltage range to 20VDC or the next above whichever is available on your multi-meter.
The article discusses can a bad alternator cause transmission problems. Hope the mentioned information was useful. If you have any queries with the information mentioned then please comment below we will get back to you as soon as possible.


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Method for diagnosing GH deficiency
The present invention relates to a method and kit for diagnosing GH (growth hormone) deficiency, in particular isolated growth hormone deficiency II (IGHD II). The method comprises the steps of analysing the missense mutation G6191 to T in exon 4 of GH-1 which changes valine 110 to phenylalanine.
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This application claims priority to U.S. Provisional Application No. 60/288,190, filed May 02, 2001.FIELD OF THE INVENTION
The present invention relates to a method and kit for diagnosing GH (growth hormone) deficiency, in particular isolated growth hormone deficiency II (IGHD II).BACKGROUND OF THE INVENTION
The majority of cases with isolated growth hormone deficiency (IGHD) are idiopathic (1). Monogenetic recessive inheritance of IGHD was shown to be caused by complete deletions of the GH-1 (IGHD IA)(2) and, more recently, by nonsense mutations of the GHRH receptor gene (3). Dominant transmission (IGHD II) was exclusively found in the presence of GH-1 splice site mutations which cause skipping of exon 3 (4,5). This in-frame deletion results in the loss of 40 amino acids and a presumably misfolded de132-71 GH. The prevalence of such mutations in families with IGHD II is high, up to 100% (6). The mechanism of the dominant negative effect of the mutant protein in only partly understood (7). In-vitro studies suggested cell-specific mechanisms in neuro-endocrine cells which included insufficient storage and secretion of the wild-type GH in the presence of the de132-71GH (8,9). Seven different splice site mutations in intron 3 of GH-1 have been reported (4,5,10–13). Because of the very compact gene structure of the GH-1, splicing is also affected by point mutations outside the conserved splicing sites (14). In addition, two GH-1 missense mutation (P89L and R183H) were recently implicated in IGHD II (15,16).SUMMARY OF THE INVENTION
The present invention provides novel markers for the diagnosing IGHD II. These markers provide early and accurate diagnosis of affected children. The present inventors have found that not only splice site mutations causing skipping of exon 3 of GH-1 but also GH-1 missense mutations result in a mutant GH with a dominant negative effect. Thus it is very important to also investigate children with suspected GH-deficiency for missense mutations.
In a first aspect, the invention relates to a method for diagnosis of autosomal dominantly inherited isolated GH deficiency (IGHD II) in a patient sample, comprising in vitro analysing the presence or absence of the novel missense mutation G6191 to T in exon 4 of GH-1 which changes valine 110 to phenylalanine. Preferably, the method also comprises analysing the presence or absence of GH-1 splice site mutations causing skipping of exon 3 of GH-1. In one preferred embodiment the splice site mutation is the novel +2T to C transition of the second base of the intron 3 donor splice site. Thus, the present invention provides two novel disease markers for IGHD II.
The method of the invention preferably comprises amplification of the GH-1 gene of the patient or fragments derived from the GH-1 gene. Preferably, the intron 3 and/or exon 2–5 are amplified. In a preferred embodiment, the method comprises PCR amplification of the GH-1 gene of the patient and nested PCR of overlapping constituent fragments of the GH-1 gene of the patient. The amplified fragments may be restriction enzyme digested or directly sequenced for detection of said mutations.
In a second aspect, the invention provides a kit for diagnosis of autosomal dominantly inherited isolated GH deficiency (IGHD II) in a patient sample, comprising means for analysing the presence of absence of the missense mutation is G6191 to T in exon 4 of GH-1 which changes valine 110 to phenylalanine.
The means may comprise reagents, primers etc for analysing a part of the GH-1 gene which includes this single nucleotide polymorphism. Preferably, the kit also comprises means for analysing the presence or absence of GH-1 splice site mutations causing skipping of exon 3 of GH-1. The splice site mutation is preferably a +2T to C transition of the second base of the intron 3 donor splice site.
The kit of the invention may comprise one or more specific GH-1 primer pairs selected from GH3.2 (nt 6578–6600), GH5.1 (nt 5503–5525); GH5.2 (nt 5555–5577), GH3.4 (nt 6547–6568); GH5.7 (nt 581–5835), GH3.7 (nt 6121–6140) and the following sequencing primers GS5.8 (nt 5629–5648), GS3.8 (6495–6515). Alternatively to the sequencing primers, the kit may comprise one or more of the following restriction enzymes MvnII, N1aIII, DdeI, MaeII.
Autosomal dominantly inherited isolated GH deficiency (IGHD II) is caused by mutations of GH-1 which alter the normal structure of GH. We studied 16 familial cases and one sporadic case with IGHD II from one Dutch and 4 German families by direct sequencing of PCR amplified gDNA and ectopic transcript analysis of lymphocyte mRNA. In addition, the clincal data of the affected individuals were analyzed. Two previously reported mutations and one novel splice site mutation in intron III of GH-1 (+1G to C, +1G to A and new: +2T to C) were detected which cause exon 3 skipping. We also discovered a novel G6191 to T missense mutation in exon 4 of GH-1 which changes valine 110 which is highly conserved in mammalian and several non-mammalian GH to phenylalanine. Splicing of the primary RNA transcript was not affected by this mutation which is very likely to alter the normal GH structure at the protein level.
The onset of growth failure was earlier and the degree more severe in the affected children with GH-1 splice site mutations in comparison to those with the GH-1 missense mutation. In addition, the severity of the phenotype was inter-individually very variable, even within the same family. The age at diagnosis was between 0.8 and 9.6 years (median 5.1), height at diagnosis was between −2.5 and −8.1 SDscore (median −4.0). Most of the children were lean at diagnosis with a BMI ranging from −1.7 to +3.3 SDscore (median −0.4). The 5 affected adults had final heights between −1.8 and −4.5 SDscore (median −3.6), centripetal obesity and muscular hypotrophy. Before therapy, IGF-I and IGFBP3 serum levels of all affected children were severely diminished (median IGF I 15.1 μg/L, median IGFBP3 910 μg/L). The maximum GH peak in a total of 25 stimulation tests was between 0.1 and 5.0 μg/L (median 0.9) indicating severe GH deficiency. The height of the adenohypophysis studied by MRI was normal in 2 affected children and mildly decreased in 2 others. Substitution with GH resulted in good catch-up growth in all treated children. The discrepancy between the very homogeneous hormone data proving severe GH- and IGF-I deficiency and the high variability of growth failure, even within the same family, suggests that the onset and the predominance of growth hormone dependent growth during infancy is individually different. Children with severe GH- and IGFI deficiency, but normal size of the adenohypophysis should be examined for GH-1 splice site and missense mutations.
The invention will be described more closely below in association with the accompanying drawings, in which:
The pedigrees of the five families (No. 1 to 5) are shown in
GH serum levels were measured in different clinical centers by several assays (RIA, ELISA, EIA) which had the same cut-off level of 10 μg GH/L for the normal response to stimulation. IGF-I and IGFBP3 concentrations in Families 1, 2, 3 and 5 were determined using the same assays by Blum et al. (18).
DNA and RNA Extraction
Genomic DNA was extracted from 5 ml frozen EDTA blood using an extraction kit (Genomix Blood Scale-Up, Talent, Triest, Italy) which was based on chloroform extraction after initial blood lysis. Total RNA from peripheral lymphocytes was extracted according to the method described by Chomozynski and Sacchi (19).
For the reverse transcription reaction, the used primer corresponded to nucleotides 6578–6600 (GH3.2) of the reported GH-1 sequence (20). The PCR was performed using GH3.2 and the upstream primer 5503–5525 (GH5.1). The up-stream primer of the nested PCR corresponded to the nucleotides 5555–5577 (GH5.2) and the down-stream primer to 6547–6568 (GH3.4). For restriction digest analysis with MvnII, N1aIII and DdeI, the nested PCR was performed with the upstream primer GH5.7 (5816–5835) and the downstream-primer GH3.7 (6121–6140). The used sequencing primers were GS5.8 (5629–5648) and GS3.8 (6495–6515).
RT-PCR of RNA
RNA (5 μg) was reverse transcribed in PCR buffer and the total cDNA was amplified by nested PCR as previously described (5). The PCR product (10 μl of the reaction volume) were electrophoresed on 8% PAGE.
PCR of Genomic DNA
Genomic DNA was amplified by nested PCR. The first PCR was performed with 0.2 μg gDNA, 100 pmol of each primer GH5.1 and GH3, 2.5 U of Taq DNA polymerase (Qiagen, Hamburg, Germany), 0.2 mmol/1 of each dNTP in Qiagen PCR buffer with a final volume of 50 μl. The reaction mixture was cycled 30 times (95° C., 60 s; 65° C., 60 s; 72° C., 90 s). An aliquot of this reaction (0.2 μl) was amplified in the nested PCR using the up-stream primer GH5.2 and the down-stream primer GH3.4 or alternatively (for restriction analysis) the sense-primer GH5.7 and the anti-sense primer GH3.7.
The 325 bp fragment of GH-1 (5816–6140) containing the complete intron 3 was digested with 20 U MvnII or with 20 U of N1aIII or with 10 U of DdeI (Boehringer Mannheim, Germany) in a volume of 30 μl containing 10 μl PCR product for 3 hrs. The 1014 bp fragment of GH-1 (5555–6568) containing the genomic sequence from exon 2 to exon 5 was digested with 4 U MaeII (Boehringer Mannheim, Germany) under the same conditions. The fragments were visualized by ethidium bromide staining after run on an 8% PAGE.
PCR products were directly double-stranded sequenced with the Thermo Sequenase cycle sequencing kit containing 7-deaza-dGTP. The reaction was performed according to the manufacture's recommendations (Amersham, Germany). The equencing primers were 5′-labelled with IR-800 fluorescent dye. The products were run under denaturing conditions on a Li-COR DNA automatic sequencer 4200.
Direct sequencing of the PCR-amplified genomic DNA resulted in the detection of a heterozygote point mutation of the first base of the donor splice site of intron 3 in the affected individuals of Families 1, 4 and 5. In detail, we found a G to A transition in Family 1 and the G to C transversion reported previously by us in Families 4 and 5 (5,17). A new splice site mutation with a T to C transition of the second base of the intron 3 donor splice site was detected in Family 2. Restriction fragment analysis of a 327 bp DNA fragment (5816–6140) containing the complete intron 3 with N1aIII (Family 1) and MvnI (Family 2) (
In Family 3, we detected a novel heterozygous point mutation in exon 4 with a G to T transversion at position 6191. Co-segregation with GH deficiency were proven by restriction fragment analysis with MaeII demonstrating heterozygote loss of the MaeII recognition site in all affected individuals (
The clinical characteristics of the affected children at the time of diagnosis are summarized in Table 1.
The SDscores were taken from Prader et al. (22). For better comparison of the genotype-phenotype-relation, the clinical data from the children with GH-1 splice site mutations (Families 1, 2, 4 and 5) and from the children affected by the GH-1 missense mutation (Family 3) are shown separately. The age at diagnosis and the degree of short stature were very variable in members of the same family as illustrated in
The stimulated GH levels were very low in all tested children regardless of the stimulus (Table 3). A GH level above 3 μg/L was reached in 3 of 25 stimulation tests (Table 3).
Therapy with 0.17 mg/kg rhGH sc weekly has been performed in 10 children for more than two years. The median height velocity during the first 2 years of therapy increased to 10, 0 cm/year (range 7.0 to 12.5) which was equivalent of a median simplification of the growth velocity by 2.1 fold (range 1.7 to 3.6). MR imaging of the hypophysis showed normal morphology and normal adenohypophysal height according to Argyropoulou et al. (23) in 2 affected children from Families 2 and 5 (−0.5 and −0.6 SDS) and a normal hypophysis with mildly reduced height in 2 children from Families 1 and 2 (−2.5 and −2.6 SDS) and in one adult (Family 1). The 5 affected adults with GH-1 splice site mutations (4 females) had short stature −3.6 (−2.7 to −4.2), centripetal obesity, muscular hypotrophy, but normal fertility. The IGF-I serum levels were severely reduced (Table 2). The mother with V110F GH had short normal stature (−1.8 SDS), but also centripetal obesity and muscular hypotrophy. Her seven pregnancies were reportedly uneventful.
All affected individuals of the five families whose pedigrees suggested an autosomal dominant transmission of IGHD carried a deleterious point mutation of GH-1 suggesting a very high prevalence of these mutations in IGHD II. One novel splice site mutation found in one family affected the highly conserved second base of the intron 3 donor splice site (+2T to C). The predicted effect of this mutation as it was shown for mutations of the first base of intron 3 is the skipping of exon 3 during splicing (4,5). The resultant de132-71 GH exerts a dominant negative effect on the wild-type GH which is cell-specific and not observed in non-secretory cell types like EBV-transformed lymphocytes (7) or COS-cells (8,9). Heterodimer formation between wild-type GH and de132-71 GH which lacks one cysteine at position 53 was the first hypothetical proposal for the dominant negative effect (4). This theory has recently been questioned by the finding that the recombinant double mutant de132-71,C165A GH which lacks the unpaired cysteine at position 165 had the same effect in-vitro (9). Both, de132-71 GH and wild-type GH do not accumulate in neuroendocrine cell lines indicating a decrease in intracellular stability (9) whose molecular basis is still unknown (24). In this context, it is of importance that missense mutations of the GH-1 also result in a mutaul GH with a dominant negative effect.
The present inventors report for the first time the V110F mutation of GH-1. Its genetic basis is a C to T transition in a CpG dinucleotide which is a general hotspot for mutations in vertebrate genomes (25). This mutation changes a valine which is completely conserved in mammalians, and in some amphibians and birds, to phenylalanine. Valine is located next to the N-terminal beginning of the third alpha-helix and integrated in the closely packed core of the four-α-helix-bundle of GH (26). The more bulky phenylalanine at this position is very likely to interfere with the normal folding of GH. Two other GH1 missense mutations which co-segregate with IGHD II were recently reported: P89L and R183H (15, 16). Similar to V110F, both mutations change highly conserved amino acids. Proline 89 forms a kink in the second α-helix of GH which leucine is not able to form (24). Arginine 183 is next to the disulfide bond of cysteine 182 whose formation may be disturbed by the more bulky histidine (24). However, the effect of the two missense mutations in cultured neuro-endocrine cells has not yet been shown.
In the past, screening for GH-1 defects was performed if severe growth failure with a height below −4.5 SDS at diagnosis were present (6). Severe short stature according to this definition was only present in one third of our affected individuals at diagnosis indicating that growth failure in IGHD II is less severe than would be expected. The children with the splice site mutations were younger and shorter at diagnosis than their counterparts with the missense mutation. Moderate growth failure was also reported from the family with the P89L mutation (16). In addition, we observed in the three families in which more than one child was affected a pronounced intrafamilial variability between siblings in both mutation groups with height differences exceeding 3.0 SDscore. This variability in growth did not correlate with the severity of growth hormone or IGF-I deficiency because the hormone levels were very low in all tested subjects including those affected individuals with the highest growth velocity and only minor growth failure. There is no substantial evidence for a course of slow progression of GH deficiency in IGHD II like it was described for the dominantly inherited vasopressin deficiency (24). Other factors than systemic GH- and IGF-I-levels must be responsible for the differences in growth failure. These unknown factors obviously modulate the start and predominance of GH dependent growth. Some of these unknown factors may also be involved in the high variability of growth failure reported in Laron syndrome (27).
Data on the systematic examination of the pituitary anatomy in monogenetic disorders are scarce (29). Approximately 50% of the hormone-producing cells of the anterior pituitary are somatotropic cells (29). Recent MRI observations in children with idiopathic GHD suggested a positive relationship of the volume of the adenohypophysis and the secretory GH capacity (30). This is not the case in IGHD II: the 4 children examined by MRI showed a normal adenohypophysis in 2 cases, mild hypoplasia in the two others. Normal size of the anterior hypophysis was also reported in two children affected with IGHD IA suggesting that the presence of GH is not a pre-requisite for normal size of the adenohypophysis (31). Therefore, the combination of normal or almost normal height of the adenohypophysis in the presence of severe GH and IGF-1 deficiency is highly suggestive of the presence of a causative GH-1 mutation. In such cases, the molecular diagnosis establishes the basis for genetic counselling and for the recommendation of a live-long substitution with GH.
- (1) Pfäffle R, Blankenstein O, Wuller S, Heimann K, Heimann G. 2000 Idiopathic growth hormone deficiency: a vanishing diagnosis? Hormone Res. 53 (Suppl 3); 1–8.
- (2) Phillips III S A, Hjelle B, Seeburg P H, Zachmann M. 1981 Molecular basis for familial isolated growth hormone deficiency. Proc Natl Acad Sci USA. 78:6372–6375.
- (3) Wajnrajch M P, Gertner J M, Harbison M D, Chua S C Jr, Leibel R L. 1996 Nonsense mutation in the growth honnone-releasing hormone receptor causes growth failure analogous to the little mouse. Nat Genet. 12:88–90.
- (4) Cogan 113, Phillips III S A, Sakati N, Frisch H, Schober E, Milner D. 1993 Heterogenous growth hormone (GH) gene mutations in familial GH deficiency. J Clin Endocrinol Metab. 76:1224–1228.
- (5) Binder G and Ranke M B. 1995 Screening for growth hormone (GH) gene splice-site mutations in sporadic cases with severe isolated GH deficiency using ectopic transcript analysis. J Clin Endocrinol Metab. 80:1247–1252.
- (6) Wagner J K, Eble A, Hindmarsch P C, Mullis P E. 1998 Prevalence of human GH-1 gene alterations in patients with isolated growth hormone deficiency. Ped Res. 43:10 5–110.
- (7) Binder G, Brown M, Parks J S 1996 Mechansims responsible for dominant expression of human growth hormone gene mutations. J Clin Endocrinol Metab. 81:4047–4050.
- (8) Hayashi Y, Yarnamoto M, Ohmori S, Kamijo T, Ogawa M, Sco H 1999 Inhibition of growth hormone (GH) secretion by a mutant G11–1 gene product in neuroendocrine cells containing secretory granules: an implication for isolated GH deficiency inherited in an autosomal dominant manner. J Clin Endocrinol Metab. 84:2134–2139.
- (9) Lee M S, Wajnrajch N T, Kirn S S, et al. 2000 Autosornal dominant growth hormone (GH) deficiency Type II: The de132-71-GH deletion mutant suppresses secretion of wild-type GH, Endocrinology. 141:883–890.
- (10) Cogan J D, Ramel, B, Lehto M, et al. 1995 A recurring dominant negative mutation causes autosomal dominant growth hormone deficiency—a clinical research center study. 80:3591–3595.
- (11) Cogan J D, Prince M A, Lekhakula S, Bundey S, Futrakul A, McCarthy E M, Phillips S A 3rd. 1997 A novel mechanism of aberrant pre-mRNA splicing in humans. Hum Mol Genet. 6:909–912.
- (12) Misarelli C, Herrera L, Mericq V, Carvallo P. 1997 Two different splice site mutations in the growth hormone gene causing autosomal dominant growth hormone deficiency. Hum Genet. 101:113–117.
- (13) Hayashi Y, Kamijo T, Yamamoto M, et al. 1999 A novel mutation at the donor splice site of intron 3 of the GH-1 gene in a patient with isolated growth hormone deficiency. Growth Horm IGF Res. 9:434–437.
- (14) McCarthy E M, Phillips J A 3rd, 1998 Characteriaztion of an intron splice enhancer that regulates alternative splicing of human GH pre-mRNA. Hum Mol Genet. 7:1491–1496.
- (15) Wajnrajch M P, Dannics P, Kim S, Gertner J M, Moshang T, Leibel R L. 1997 Pathophysiology of autosomal dominant GH deficiency [Abstract]. Proc 79th Mect of The Endocrine Society; PO 1–084.
- (16) Duquesnov P, Simon D, Netchine 1, et al. Familial isolated growth hormone deficiency with slight height reduction due to a heterozygote mutation in GH gene [Abstract]. Proc 80th Meeting of The Endocrine Society; P02–202.
- (17) Massa G G, binder G, Oostdijk W, Ranke M B, Wit J M. 1998 De novo mutations of the growth hormone gene: an important cause of congenital isolated growth hormone deficiency? Eur J Pediatr. 157:272–275.
- (18) Blum W F, Albertsson-Wikland K, Rosberg S, Ranke M B. 1993 Serum levels of insulin-like growth factor I (IGF-1) and IGF binding protein 3 (1WBP-3) reflect spontaneous growth hormone secretion. J Clin Endocrinol Metab. 76:1610–1616.
- (19) Chomczynski P and Sacchi N. 1987 Single-step method of RNA isolation by acid Guanidinium Thiocyanate-Phenol-Chloroform extraction. Anal Biochem. 162:156–159.
- (20) Chen E Y, Liao Y-C, Smith D H, Barrera-Saldana H A, Gelinas R E, Seeburg P H. 1989 The human growth hormone locus: Nucleotide sequence, biology, and evolution. Genomics. 4:479–497.
- (21) Watakabe A, Tanaka K, Shimura Y. 1993 The role of exon sequences in splice site selection. Genes Dev. 7:407–418.
- (22) Prader A, Largo H R, Molinari L, Issler C. 1989 Physical growth of Swiss children from birth to 20 years of age. HeIv Paediat Acta. [Suppl]. 513–3 1.
- (23) Argyropoulou M, Perignon F, Brunelle F, Brauner R, Rappaport R, 1991 Height of normal pituitary gland as a function of age evaluated by magnetic resonance imaging in children. Pediatr Radiol. 21:247–249.
- (24) Dannies P S. 2000 Protein folding and deficiencies caused by dominant-negative mutants of hormones. Vitam Horm. 58:1–26.
- (25) Cooper D N, Krawczak M, Antonorakis S E. 1995 In; Scriver C R, Beaudet A L, Sly W S, Valle D, eds. The metabolic and molecular bases of inherited disease. 7th ed. New York: McGraw-Hill; 259–291.
- (26) Ultsch M E, Somers W, Kossiakoff A A, deVos A M. 1994 The crystal structure of affinitymatured human growth hormone at 2 A resolution. J Mol Biol, 236:286–299.
- (27) Wood K A, Savage M O. 1996 Laron syndrome: typical and atypical forms. Baillieres Clin Endocrinol Metab. 10:371–387.
- (28) Murray R A, Maheshwari H G, Russell E J, Baumann G. 2000 Pituitary hypoplasia in patients with a mutation in the growth hormone-releasing hormone receptor gene. MNR. 21:685–689.
- (29) Thorner M O, Vance M L, Laws E F, Horvath E, Kovacs K. 1998 The anterior pituitary. In: Wilson J D, Foster D, Kronenberg F A I, Larsen P R, eds. William's Textbook of Endocrinology. 9th ed, Philadelphia: ViB Saunders; 256.
- (30) Hamilton J, Blaser S, Daneman D. 1998 MR imaging in idiopathic growth hormone deficiency. AM. 19:1609–1615.
- (31) Zucchini S, Ambrosetto P, Baroncini C, Cacciari E. 1996 Normal pituitary size in two patients with growth hormone gene deletion. J Ped Endocrinol Metab. 9:545–548.
1. A method for diagnosis of autosomal dominantly inherited isolated GH deficiency (IGHD II) in a patient, comprising directly analyzing a nucleic acid sample provided from the patient for the presence or absence of a T at nucleotide position 6191 in exon 4 of the GH-1 gene, and determining that the patient from which the sample is provided has autosomal inherited IGHD II when a T is present at nucleotide position 6191 in exon 4 of the GH-1 gene.
2. A method according to claim 1, also comprising analyzing the sample for the presence or absence of a GH-1 splice site mutation causing skipping of exon 3 of the GH-1 gene.
3. A method according to claim 2, wherein the splice site mutation is +2T to C transition of the second base of the intron 3 donor splice site.
4. A method according to claim 1, wherein the sample is from a patient having a normal size of adenohypophysis.
5. A method according to claim 1, wherein the directly analyzing step comprises amplifying the GH-1 gene or fragments derived from the GH-1 gene.
6. A method according to claim 5, wherein intron 3 and/or exon 2–5 are amplified.
7. A method according to claim 5, wherein the amplifying step comprises PCR amplification of the GH-1 gene and nested PCR of overlapping constituent fragments of the GH-1 gene.
8. A method according to claim 1, wherein the directly analyzing step comprises restriction enzyme digesting amplified fragments.
9. A method according to claim 5, wherein the directly analyzing step further comprises sequencing of amplified fragments.
10. A method according to claim 7, wherein the amplifying step is conducted with one or more specific GH-1 primer pairs wherein the primers are selected from the group consisting of GH3.2 (nt 6578–6600), of the GH1 gene GH5.1 (nt 5503–5525); of the GH1 gene GH5.2 (nt 5555–55 77), of the GH1 gene GH3.4 (nt 6547–6568); of the GH1 gene GH5.7 (nt 5816–5835), of the GH1 gene and GH3.7 (nt 6121–6140) of the GH1 gene.
11. A method according to claim 9, wherein the sequencing is conducted with the sequencing primers GS5.8 (nt 5629–5648), of the GH1 gene and GS3.8 (nt 6495–6515) of the GH1 gene.
12. A method according to claim 8, wherein the digesting is conducted with one or more of the restriction enzymes MvnII, NIaIII, DdeI, and MaeII.
13. A method according to claim 2, wherein the directly analyzing step comprises amplifying the GH-1 gene or fragments derived from the GH-1 gene.
14. A method according to claim 3, wherein the directly analyzing step comprises amplifying the GH-1 gene of the patient from which the sample is obtained or fragments derived from the GH-1 gene.
15. A method according to claim 6, wherein the amplifying step comprises PCR amplification of the GH-1 gene and nested PCR of overlapping constituent fragments of the GH-1 gene.
16. A method according to claim 13, wherein the amplifying step is conducted with one or more specific GH-1 primer pairs wherein the primers are selected from the group consisting of GH3.2 (nt 6578–6600), of the GH1 gene GH5.1 (nt 5503–5525); of the GH1 gene GH5.2 (nt 5555–5577), of the GH1 gene GH3.4 (nt 6547–6568); of the GH1 gene GH5.7 (nt 5816–5835), of the GH1 gene and GH3.7 (nt 6121–6140) of the GH1 gene.
17. A method according to claim 15, wherein the amplifying step is conducted with one or more specific GH-1 primer pairs wherein the primers are selected from the group consisting of GH3.2 (nt 6578–6600), of the GH1 gene GH5.1 (nt 5503–5525); of the GH1 gene GH5.2 (nt 5555–5577), of the GH1 gene GH3.4 (nt 6547–6568); of the GH1 gene GH5.7 (nt 5816–5835), of the GH1 gene and GH3.7 (nt 6121–6140) of the GH1 gene.
- Lucentini, J. The Scientist. Dec. 2004, p. 20.
- Wajnrajach et al, Pathophysiology of Autosomal Dominant GH Deficiency, Programs and Abstracts from the 79th Annual Meeting of The Endocrine Society, Minneapolis, MN, Abstract PI-84, p. 155 (1997).
- Pfäffle et al, Horm. Res., 53(Suppl 3):1-8(2000).
- Phillips et al, Proc. Natl. Acad. Sci. USA, 78:6372-6375 (1981).
- Wajnarajch et al, Nature Genetics, 12:88-90 (1996).
- Cogan et al, Journal of Clinical Endocrinology and Metabolism, 76(5):1224-1228 (1993).
- Binder et al, Journal of Clinical Endocrinology and Metabolism, 80(4):1247-1252 (1995).
- Wagner et al, Pediatric Research, 43(1):105-110 (1998).
- Binder et al, Journal of Clinical Endocrinology and Metabolism, 81(11): 4047-4050 (1996).
- Hayashi et al, Journal of Clinical Endocrinology and Metabolism, 84(6):2134-2139 (1999).
- Lee et al, Endocrinology, 14(3):883-890 (2000).
- Cogan et al, Journal of Clinical Endocrinology and Metabolism, 80(12):3591-3595 (1995).
- Cogan et al, Human Molecular Genetics, 6(6):909-912 (1997).
- Missarelli et al, Human Genetics, 101:113-117 (1997).
- Hayashi et al, Growth Hormone and IGF Research, 9:434-437 (1999).
- McCarthy et al, Human Molecular Genetics, 7(9):1491-1496 (1998).
- Duquesnov et al, Familial isolated growth hormone deficiency with slight height reduction due to a heterozygote mutation in GH gene, (Abstract), Proc. 80th Meeting of The Endocrine Society, P2-202 (1998).
- Massa et al, Eur. J. Pediatr., 157:272-275 (1998).
- Blum et al, Journal of Clinical Endocrinology and Metabolism, 76(6): 1610-1616 (1993).
- Chomczynski et al, Analytical Biochemistry, 162:156-159 (1987).
- Chen et al, Genomics, 4:479-797 (1989).
- Watakabe et al, Genes & Development, 7:407-418 (1993).
- Prader et al, Helv. Paediat. Acta. (Suppl.), 43:3-125 (1998).
- Argyropoulou et al, Pediatric Radiologyi, 21:247-249 (1991).
- Danies, Vitamins and Hormones, 58:1-26 (2000).
- Cooper et al, The Metabolic and Molecular Bases of Inherited Disease, 7th Edition, New York: McGraw-Hill, pp. 259-291, undated.
- Ultsch et al, J. Med. Biol., 236:286-299 (1994).
- Woods et al, Balliere's Clinical Endocrinology and Metabolism, 10(3):371-383 (1996).
- Murray et al, Am. J. Neuroadiol., 21:685-689 (2000).
- Thorner et al, Williarn's Textbook of Endocrinology, 9:249-340 (1998).
- Hamilton et al, Am. J. Neuroadiol., 19:1609-1615 (1998).
- Zucchini et al, Journal of Pediatric Endocrinology & Metabolism, 9:545-548 (1996).
International Classification: C12Q 1/68 (20060101); C12P 19/34 (20060101); C07H 21/02 (20060101); C07H 21/04 (20060101);

domain: medical


text:
A very interesting concept – three possible outcomes for the same couple. We’ve all questioned the ‘what ifs’ in our lives, so this novel has a go at unpicking the actual outcomes of decisions made over the span of an entire lifetime. What keeps you flicking the pages in this book (and I did read it very quickly) is the short chapters and the unusual concept. I would have liked for it to be executed with a little more finesse.
Eva and Jim meet at a chance encounter while at University. But while the first time they see each other doesn’t change, the way their lives play out following that moment is explored in three alternatives. In one, they stay together, in the second, they keep missing each other, while in the third, things go rather disastrously wrong, at least at first. We follow both of them from their twenties through to their seventies, from London to New York to Paris, and untangle the confusions and delights of two lives, lived to the full, and the effect that certain decisions have on them and those close to them. It’s a clever premise, and it’s certainly engaging to be taken to many different locations, intimately described, and to have the opportunity of seeing the parallel universes of two people and the way they shift and fluctuate towards and away from each other.
I saw Laura Barnett at a reading of her next book, Greatest Hits, which also sounds interesting. In her new novel, she explores the idea of a life lived through one day, and the memories and ideas that this day throws up allows the reader to see their whole life. In the interview, Laura said she didn’t have a carefully mapped out plot for The Versions of Us with lots of post-it notes or charts, that it was all in her head. I would say that this is perhaps clear from the reading of it. While the stories were certainly interesting, I wasn’t particularly compelled or surprised by what happened in each of the threads, and the different plot points didn’t necessarily drive the novel forward. What does, of course, is the varying relationship between the two central characters, and the way the outcomes are different. It also perhaps explained the missed facts and time inconsistencies that were littered throughout. The method of narrative is a clever device, and it is a clever book, but I was disappointed that more wasn’t made of the interweaving, as it could have allowed for some really unusual storytelling.
The other issue is, in itself, the threading together of three narratives. Because the chapters are so sparse, I found myself losing track of which daughter or son was which, the main problem being that I no longer cared as much what happened to them. This was especially the case with the ‘extra’ characters, that really didn’t get fleshed out enough to make it off the page. It is certainly a difficult thing to do, threading all of these narratives together, but I wonder if giving us longer chapters as the book progressed would have allowed us to be better immersed into each specific world, as I found myself flitting through the book, not very invested. The other problem that this multiple narrative throws up is the need to ‘tell’ so much. With gaps of months or even years between each episode, we find the character quite awkwardly reflecting on something that doesn’t always seem natural, simply because the reader needs to be filled in on what has come before. I can understand that this was a difficulty in leaving gaps, but perhaps it would have been nice to tackle them in slightly different ways each time, to avoid the ‘she/he remembered…’ feel that gets a bit repetitive. It also meant that feelings were often reported rather than experienced, which again left me feeling emotionally distant from the character’s journey. Perhaps two threads might have meant that the stories could be more intimate and fully developed, rather than spread so thinly between three.
Her prose is flowing and smooth, with the occasional touch of beautiful phrase. This gives it a nice pace, so that in between your brain catching up with who is who and what was happening last time you saw them, there are elegant descriptions that I found delightful. In fact, the nuance of language just edges it out of being a beach read, as it doesn’t (always) fall for easy clichés and offers a far more subtle exploration of relationships (in all their forms) than you would expect from a different kind of book.
To be clear, this is a very engaging and interesting novel, and I did really like the interplay between the character’s lives. It’s an interesting concept, as we so often cite ‘timing’ as such an important factor in relationships, that to see the actual result of three different timings between the same two people is a very interesting exercise. I just would have liked to be more emotionally engaged with the story.
#writing #bookreview #review #description #prose #literature #creativity #article #laurabarnett #theversionsofus #novel

domain: library


text:
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Internal Audit of Results-Based Management
- Acronyms and Initialisms
- Executive Summary
- 1.0 Background
- 2.0 Audit Objective, Scope, Approach, and Criteria
- 3.0 Main Audit Findings and Recommendations
- Appendix A: List of Recommendations and Management Action Plan
- Appendix B: List of Results-Based Management Instruments
- Appendix C: Results-Based Management Terminology at the Investment, Intermediate, and Agency Levels
Acronyms and Initialisms
- Chief Financial Officer Branch
- Canadian International Development Agency
- Geographic Programs Branch
- Investment Monitoring and Reporting Tool
- Multilateral and Global Programs Branch
- Monitoring and Reporting Tool
- Program Alignment Architecture
- Performance Measurement Framework
- Partnerships with Canadians Branch
- Results-Based Management
- Strategic Policy and Performance Branch
In accordance with the 2011-2014 Risk-based Audit Plan, the Office of the Chief Audit Executive at the Canadian International Development Agency (CIDA) conducted an internal audit of Results-Based Management (RBM). The objective was to provide reasonable assurance that the processes and controls in place to support RBM at CIDA are adequate and effective in support of decision making, accountability, and oversight.
RBM is a life-cycle approach to management that integrates strategy, people, resources, processes, and measurements to improve decision making, transparency, and accountability. The approach focuses on implementing performance measurement, learning, and adapting, as well as reporting performance, in order to achieve outcomes.
Strategic Policy and Performance Branch (SPPB) is the functional lead for RBM at CIDA, while the three program branches—Geographic Programs Branch (GPB), Multilateral and Global Programs Branch (MGPB) and Partnerships with Canadians Branch (PWCB)—are the main users of RBM to enable the achievement of development results.
The Agency's 2008 RBM Policy, Performance Management Agreements, and certain oversight bodies provide clear accountability with respect to RBM. Along with these robust accountability mechanisms, RBM leadership and understanding are indicative of a well-engrained RBM culture at CIDA.
At the Agency level, alignment of the Performance Measurement Framework (PMF) with the Program Alignment Architecture (PAA) provides assurance that the Agency's reporting to Parliament is in line with the expected results committed to in the Report on Plans and Priorities. Performance Management Strategies for CIDA's three thematic priorities exist, and although they can generally be traced to the PAA, they are not explicitly aligned with the PAA.
RBM instruments at the investment and intermediate levels are in use in GPB, and are used to inform decision making and reporting. In MGPB and PWCB, RBM takes place to inform decision making and reporting principally at the investment level from which performance information is not systematically channelled upward to the Agency level, although compensating measures exist to support external reporting. In all three program branches, opportunity exists to enhance the efficiency and effectiveness of RBM instruments.
Although some instruments are designed to provide management with all facets of performance information, including risk and financial information, in practice, integrated reporting is not being done at the Agency, intermediate, or investment levels. Furthermore, the lack of a standardized classification of indicators and the inconsistent use of the Agency's repository of performance information, combined with the varied and frequent requests for information, lead to an inefficiency of data collection and reporting.
Performance-related information is used by all three program branches to support decision making and course corrections at the investment level. However, an opportunity exists to strengthen linkages between Agency-level performance reporting and planning.
CIDA has implemented a number of RBM processes that are reinforced by a well-ingrained RBM culture. Although the audit found there were areas for improving RBM controls, compensating measures are in place to support accountability requirements, such as external reporting.
There are a number of initiatives underway that may help address some of the weaknesses noted in this report. Included among them are the work on "headline results and indicators," the review of the PAA, and a streamlining of the Monitoring and Reporting Tool (MRT).
Statement of Conformance
In my professional judgment as the Chief Audit Executive, this audit was conducted in conformance with the Institute of Internal Auditors' International Standards for the Professional Practice of Internal Auditing and with the Internal Auditing Standards for the Government of Canada, as supported by the results of the quality assurance and improvement program. Sufficient and appropriate audit procedures were conducted, and evidence gathered, to support the accuracy of the findings and conclusion in this report, and to provide an audit level of assurance. The findings and conclusion are based on a comparison of the conditions, as they existed at the time, against pre-established audit criteria that were agreed upon with management and are only applicable to the entity examined and for the scope and time period covered by the audit.
Chief Audit Executive
CIDA's strategic outcome is "Reduction in poverty for those living in countries where CIDA engages in international development." The Agency achieves this outcome by pursuing three priority themes: stimulating economic growth, increasing food security, and securing the future of children and youth. The multidimensional nature of CIDA's results is complex, and is further complicated by the three crosscutting themes of environmental sustainability, equality between men and women, and strong governance practices.
The Agency has implemented RBM to help deliver on these expected results and priorities. CIDA's RBM policy, practices and tools are intended to support sound corporate, program, and project planning and to enable program implementation, monitoring, and evaluation, as well as the Agency's reporting to Parliament, Canadians and international stakeholders.Footnote 1 RBM has been implemented in keeping with the Treasury Board Policy on Management, Resources and Results Structures, and the principles of aid effectiveness as outlined in the Paris Declaration on Aid Effectiveness and the Official Development Assistance Accountability Act. More than just a compliance requirement, RBM supports sound management and resource-allocation decisions, thereby contributing to effective stewardship, accountability, and value for money.
The means by which CIDA's RBM objectives are operationalized varies among the program branches in accordance with their particular operating realities.
Geographic Programs Branch comprises five regional directorates, each providing development assistance in a series of specific countries or regions. These individual country or regional programs are typically aligned with a development plan created by the government of that country. Of GPB's funding, 80 percent goes to 20 countries of focus. GPB's partners may include recipient governments, multilateral institutions, non-governmental organizations, universities, associations, private corporations, and other donors.
Multilateral and Global Programs Branch focuses its efforts on building strategic relationships with multilateral and global partners to achieve development results and to address the immediate needs of crisis-affected populations. The Agency is one of many donors to a given multilateral institution, each of which maintains its own RBM regime. CIDA leverages these institutional frameworks and works through the governance bodies of these organizations to influence institutional results. CIDA contributes to the achievement of multiple thematic priorities through its investment in a given multilateral institution.
Partnerships with Canadians Branch supports development projects and programs that are designed and implemented by Canadian organizations in cooperation with their counterpart organizations in developing countries. PWCB programming is responsive in nature. That is, through a formal call-for-proposal process, Canadian civil society organizations submit proposals for funding that align with the broad objectives CIDA wishes to obtain. Projects can be multi-country in nature, and will often contribute to more than one thematic priority.
The adjacent graphic provides a breakdown of grant and contribution funding by branch. The materiality of funding heightens the importance of managing for results. The many requirements for results reporting, driven in large part by the high degree of public and political scrutiny faced by CIDA and its partners, also increases the importance of RBM.
Chart description: CIDA 2010-2011 Grants and Contributions
Approved Budget by Branch - in $ thousands
GPB-$1,214,045 (54 percent)
MGPB-$822,911 (36 percent)
PWCB-$234,749 (10 percent)
Source: 2011-2012 Branch Integrated Business Plans
The inherent complexities and materiality of CIDA programming, coupled with the significance of RBM, led the Office of the Chief Audit Executive to identify RBM as an area of high priority. Accordingly, an audit of RBM was approved in the 2011–2014 Risk-based Audit Plan.
2.0 Audit Objective, Scope, Approach, and Criteria
The objective of the audit was to provide reasonable assurance that the processes and controls in place to support RBM at CIDA are adequate and effective in support of decision making, accountability, and oversight.
The scope of the audit was limited to 2010–2011; however, to ensure the relevance of audit findings, recent RBM practices that continue to evolve were taken into consideration. The audit examined RBM practices of SPPB as the functional lead for RBM at CIDA. As well, program branches—GPB, MGPB, and PWCB—were also included in the scope in light of their roles for practising RBM.
2.3 Approach and Methodology
The audit was conducted in accordance with the Treasury Board Policy on Internal Audit and the International Professional Practices Framework of the Institute of Internal Auditors. The audit's scope and testing protocols were determined based on an analysis of risk. Interviews and documentation review were conducted during the planning and examination phases with all program branches as well as with Communications Branch and Chief Financial Officer Branch (CFOB). As well, 22 project files, selected from all three program branches using judgmental sampling techniques, were examined. Once findings were developed, they were validated with representatives of all branches. These then formed the basis of this report.
2.4 Audit Criteria
The following three lines of enquiry were used that collectively set the standard against which the audit was conducted:
- There is appropriate and effective leadership, accountability, and oversight of the Agency's performance-management regime.
- RBM tools and measures are effective, and where appropriate, are aligned with one another.
- CIDA leverages information collected through the established RBM tools to effectively support reporting.
3.0 Main Audit Findings and Recommendations
3.1 Governance and Accountability
One of the foundations of any key management practice, including RBM, is a robust governance regime that includes clear accountability for the function. In recognition of the importance of this, the audit sought to determine whether roles, responsibilities, and accountabilities related to RBM were well articulated, communicated, and understood.
The audit found that mechanisms to ensure clear accountability were robust and well entrenched. Of note is CIDA's RBM Policy (2008) developed by the Strategic Planning, Performance and Evaluation Directorate of SPPB, and readily accessible to all staff on the intranet. Accountability for the practice of RBM is clearly articulated in this policy. The policy includes a section entitled Accountability, which states that "CIDA will ensure that RBM is featured in Performance Management Agreements of its executives."
The audit also confirmed Performance Management Agreements were used to embed expectations for the implementation of RBM. Through this mechanism, executives are not only held accountable for RBM, but also for enabling the achievement of development results. While not responsible for the direct achievement of development results, the Performance Management Agreements provide a reasonable linkage between the enabling results against which managers are held accountable and the achievement of development results by CIDA's partners.
The clear documentation and guidance that define expectations with respect to RBM are complemented by a well-ingrained RBM culture across the Agency. All staff interviewed understood RBM, their RBM-related roles, as well as its importance to CIDA's operations. RBM leadership, understanding, and accountability for managing for results are all indicative of a strong RBM culture at CIDA. This culture in turn reinforces the more formal controls in this area.
Beyond individual accountability mechanisms, the audit also examined corporate governance structures used to oversee, and thus hold the organization accountable for, RBM. The audit concluded these mechanisms are appropriate and robust. Specific strengths include a strong degree of corporate leadership, process, and structures for the review and redevelopment of CIDA's PAA. Similarly, appropriate processes were found to be in place for the review and challenge of expected and actual results in CIDA's key accountability documents (i.e. Report on Plans and Priorities and Departmental Performance Report).
As well, the audit noted that various oversight structures were in place at the Agency and branch levels that contribute to accountability for RBM. At the Agency level, the members of the Management Board play an active role by reviewing and challenging the results outlined in the Annual Country Reports for CIDA's 20 countries of focus. At the branch level, the Branch Investment Review Committee within GPB reviews and challenges expected results prior to including them in project proposals submitted for approval. As part of PWCB's call-for-proposal process, subject-matter experts review and challenge expected results outlined by partners as part of their proposal submission. MGPB's Branch Oversight Committee plays an active role in reviewing institutional strategies and other strategic/policy directions, including relevant expected results.
3.2 Results-Based Management Instruments
The practice of RBM at CIDA is enabled by a wide range of instruments that allow for the identification of expected results; the measurement, capture, and analysis of actual results achieved; and the reporting of outcomes. A full compendium of these instruments is provided in Appendix B. The audit examined key instruments to determine whether they were adequate and effective in enabling RBM to be deployed across the Agency.
Further, the audit sought to determine whether there was vertical alignment of these instruments and results at the investment, intermediate, and Agency levels.Footnote 2 Vertical alignment is needed so that Agency-level expected results inform the development of lower-level expected results such that the latter are in line with the higher-order outcomes. This is necessary to avoid divergence of planned outcomes, and thus, of activities and expenditures. This alignment is also critical to ensure that results, once achieved at the lower levels, can be effectively and efficiently analyzed and aggregated in support of meaningful decision making and reporting. Simply stated, management needs to be able to answer the following questions:
- Are the investments being made on the ground the right ones, and are they relevant in the context of the higher-level outcomes?
- Are the results being achieved on the ground meaningfully and positively contributing to these higher-order outcomes whether at the intermediate or the Agency level?
- If not, how should resources be reallocated to better achieve the outcomes?
At the Agency level, the corporate PMF, the highest-order RBM instrument of the Agency and the basis for reporting to Parliament, is aligned with the PAA. This alignment provides assurance that at the highest level, the Agency's accountability reporting is in line with the expected results committed to in the Report on Plans and Priorities. However, the audit also noted that, in practice, other Agency-level instruments are in use and are more predominant in operations. Of note, Performance Management Strategies for CIDA's three thematic priorities exist and are highly referenced across the Agency's operations. They are also integrated into program-related decision-making and oversight mechanisms. While thematic priorities can be generally traced to the PAA, the thematic Performance Management Strategies and the corporate PMF are not explicitly aligned. This means that thematic results, once realized, must then be translated into a different frame—that of the corporate PMF—for accountability reporting purposes. Current efforts are underway to develop a set of Agency-level headline results and indicators, which will be anchored on the thematic priorities. These headline results are being developed to clearly articulate CIDA's performance through understandable, plain language statements and targets. A review of potential changes to the PAA is also underway and includes consideration of the headline results. It was noted that over the last three years, the Agency has implemented or modified a number of its Agency-level instruments (e.g. corporate PMF, thematic priority Performance Management Strategies). While some level of evolution is appropriate, the use of a stable, common PAA for the depiction of expected results is necessary to regularize RBM.
Results-Based Management Instruments at the Intermediate and Investment Levels
Working from the Agency-level frames and expected results, the audit identified and assessed the adequacy and effectiveness of RBM instruments at various levels. Further, the audit sought to determine whether there was alignment from the highest level to the lowest level of operations: in other words, whether Agency, intermediate, and investment-level frames and results were mutually aligned.
The audit found that, within branches, a range of instruments exists to identify expected results and measures. In GPB, RBM instruments at the investment and intermediate (i.e. program) levels exist. They are aligned with one another, and with the PAA and corporate PMF. In PWCB and MGPB, the principal level at which RBM takes place is the investment level. Although expected results are articulated in the PAA at the subprogram level (i.e. the intermediate level, as outlined in Appendix C), they were not used by PWCB and MGPB as the basis of management, monitoring, or decision making as both branches have stated that they did not add value.
MGPB's investments are fundamentally different from the projects funded by GPB or PWCB in that CIDA is one of many donors providing long-term institutional support to these institutions, along with earmarked funding for global initiatives. To this end, the branch considers the alignment between an institution's expected results and CIDA's goals. By approving CIDA funding for an institution or global initiative, CIDA shares ownership of the expected results. MGPB plays an active role in the governance and RBM regimes of the multilateral institutions, and works with them to oversee and influence them in the achievement of expected results. In this way, programming supported by MGPB aims to contribute to the achievement of CIDA's expected results. The audit noted that the process for reporting how an institution's results have contributed to achieving CIDA's development goals could be strengthened. As a result, MGPB should look for opportunities to enhance the identification, measurement, and reporting of results.
Investment Monitoring and Reporting Tool
As noted above, based on interview evidence, concerns were raised in relation to the Investment Monitoring and Reporting Tool (IMRT), which is a key tool designed to support RBM at the investment level. While considerable progress has been made to date in implementing it across the Agency and although extensive guidance and training has been provided, the use and applicability of the tool were identified as areas for improvement. Data quality and analytical ability are at risk due to the high degree of manual entry, the limited requirements for the use of standardized indicators, and limited controls over data entry. Finally, the inability to link investment results in IMRT to higher-level results, specific countries, or themes works against data mining, analysis, or efficient multidimensional reporting. Management has stated it is aware of these IMRT limitations and will work with Information Management and Technology Branch to improve the tool accordingly.
The Vice-President of SPPB should ensure that the PAA and corporate PMF are used as the single, common frame for internal planning, budgeting, and reporting and external parliamentary reporting of results. Work being done on the Agency-level thematic (e.g. headline) results and indicators should be appropriately reflected in the PAA and corporate PMF.
The Vice-President of MGPB, in collaboration with the Vice-President of SPPB, should modify the branch's existing management instruments to enhance the identification, measurement, and reporting of results.
3.3 Use of Results Information
In addition to examining the existence and alignment of results information and instruments, the audit also sought to determine whether the information produced was used in support of comprehensive, efficient, and effective reporting and decision making.
Efficiency of Data Collection and Reporting
Requests for performance information, whether ad hoc or formal, come from various sources, including Communications Branch, SPPB, the Minister's Office, the general public, and parliamentarians. The audit found that efficiency of data collection and reporting could be improved. Specifically, the Agency's existing repository of performance information is not used consistently across branches. As a result, information to respond to these requests must be retrieved (often manually) from Management Summary Reports, Annual Country Reports, annual reports, the Project Browser, or partners.
There is no classification of key performance indicators to help standardize or efficiently develop PMFs at the investment or intermediate levels. At the same time, at the investment level, file review indicated there was a high number of indicators for which data is collected: some projects had more than fifty performance indicators outlined in their investment-level PMFs. While unique indicators may be needed for certain investments, many commonalities exist, and as a result, opportunities exist for a convergence of indicators. At the present time, more than 8,000 indicators exist in the IMRT, including a vast array of similar indicators, named differently. Management has stated that efforts underway to identify headline results and indicators and to improve the MRT will also allow a standardization of indicators. However, until such time as this frame is deployed, the risk of inefficiency in data collection and reporting remains high.
In GPB, Country Strategies are used to guide the Agency's programming and project development. Those related to the 20 countries of focus are approved by the Minister. These include a suite of results aligned with CIDA's thematic priorities. The Annual Country Reports developed by GPB serve as the mechanism against which the expected results outlined in the Country Strategies are reported. Prior to the development of Country Strategies, the Agency used Country Development Performance Frameworks to guide programming and project development. Although the Country Development Performance Framework includes a detailed logic model and program-level PMF, there was limited evidence that they are currently used to support project development and approval or program reporting and accountability. Rather, as noted above, Country Strategies are used for this purpose. As such, developing and maintaining Country Development Performance Frameworks may not be an efficient utilization of Agency resources.
Integrated and Holistic Analysis
The audit also sought to determine whether mechanisms are in place to provide management with all facets of performance information, including risk and financial information. The audit found that although some instruments are designed for integrated reporting, in practice, this is not being done.
At the investment level, one of the key tools intended for the purposes of integrated reporting and analysis is the IMRT. It has been designed to consolidate all facets of performance information. Evidence of consolidated performance information was found to be most evident in GPB, where IMRT is more widely deployed. However, in some files examined, it was noted that risk information, identified in the narrative part of the IMRT's Management Summary Report, was not reflected in the risk register section of the same report. In addition to the risk register not being up to date, in some cases, it was also incomplete.
At the intermediate level, integration of all facets of performance was found to be lacking. Because PWCB and MGPB do not produce performance reports at the intermediate level, the audit focused only on the Annual Country Report, which is the primary intermediate-level performance report in GPB. The audit found that although the Annual Country Reports provide a good mechanism for the analysis and aggregation of performance results information at the country level, limited financial and risk information was included.
At the Agency level, commencing in 2011–2012, branches were required to submit a monitoring report to CFOB as part of the midyear review process. The audit examined the tools used for this purpose to determine whether the monitoring process compels the consideration of all aspects of performance. The audit found that information provided in the midyear report is focused more on the types of performance monitoring activities in use in branches than actual performance.
Using Results to Plan and Course Correct
The audit found that opportunity exists to strengthen linkages between Agency-level performance reporting and planning. Specifically, no documented evidence exists demonstrating that results information is formally or systematically used to inform Agency planning, resource allocation, or the midyear review. It is important, however, to note that interview evidence indicated that results are discussed as part of these deliberations, although these are not documented. As well, the audit noted that performance information was integrated into Agency decisions related to the Government of Canada's Deficit Reduction Action Plan exercise.
In addition, the audit noted that performance-related information is used to support decision making and course corrections at the investment level across all three branches:
- GPB uses intermediate- and investment-level results information to support its decision making at all levels and to inform Agency reporting.
- In MGPB, although RBM instruments should be modified, results information is used, for example, in investment decision making and the development of Institutional Strategies.
- PWCB investment-level results information is useful for partners and Development Officers in monitoring investments.
Reporting Against Results
Although results information informs reporting and oversight at the investment level, these results are not systematically being rolled up into Agency reporting. This is particularly the case for PWCB and MGPB, where because of the lack of intermediate frames, there are no direct channels through which information is gathered, aggregated, and reported upon. MGPB and PWCB are able to select and provide performance information that supports Agency reporting. However, there remains a risk that Agency-level reports may not be fully or systematically informed by investment-level results information.
There are clear channels for systematic, upward reporting in GPB: Management Summary Reports feed Annual Country Reports, which in turn feed the Departmental Performance Report and Development for Results Report. At the branch level, although branches prepare Integrated Business Plans, there is no requirement to report against them.
More positively, the information that is aggregated upward is used and cross-verified to feed multiple Agency-level reports, including the Departmental Performance Report, the Development for Results Report, and the Report to Parliament on the Government of Canada's Official Development Assistance.
To support efficient and effective responses to requests for performance information, the Vice-Presidents of SPPB, GPB, PWCB, and MGPB should ensure that a single repository for performance information is used that meets the needs of program branches.
The Chief Financial Officer should ensure that all facets of performance (i.e. risk, financial, and results) are integrated in the Agency's midyear review process.
Appendix A: List of Recommendations and Management Action Plan
|Proposed Management Measures
|1. The Vice-President of SPPB should ensure that the PAA and corporate PMF are used as the single, common frame for internal planning, budgeting, and reporting and external parliamentary reporting of results. Work being done on the Agency-level thematic (e.g. headline) results and indicators should be appropriately reflected in the PAA and corporate PMF.
|Jan. 31, 2014
|2. The Vice-President of MGPB, in collaboration with the Vice-President of SPPB, should modify the branch's existing management instruments to enhance the identification, measurement, and reporting of results.
|Vice-President, MGPB, in collaboration with Vice-President, SPPB
|Aug. 30, 2013
|3. To support efficient and effective responses to requests for performance information, the Vice-Presidents of SPPB, GPB, PWCB, and MGPB should ensure that a single repository for performance information is used that meets the needs of program branches.
|Vice-Presidents, SPPB, GPB, PWCB, and MGPB in collaboration with the Chief Information Officer
|Aug. 30, 2013
|4. The Chief Financial Officer should ensure that all facets of performance (i.e. risk, financial, and results) are integrated in the Agency's midyear review process.
|Chief Financial Officer
|Nov. 15, 2013
Appendix B: List of Results-Based Management Instruments
|Identification of planned results
|Measure, capture and analysis of results
Appendix C: Results-Based Management Terminology at the Investment, Intermediate, and Agency Levels
|Level in the RBM Hierarchy
- Date Modified: