What is Stress?

Prevention and Management of Stresses

Informative Poster on the Measures to be taken

VIGOSINE® : Mode of Action and Results

VIGOSINE®: Management of stresses in broilers

and laying hens

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Prevention and management of

stresses in broilers and laying hens

I. StressI.1. DefinitionI.2. What are the stress inducing

factors?

II. Chronology of possible stressesII.1. Chronology of possible stresses

for broilersII.2. Chronology of possible stresses

for laying hens

III. Physiological mechanism of stress

III.1. Alarm phaseIII.2. Resistance phase : the bird tries

to adapt to its new living conditionsIII.3. Decompensation phaseIII.4. The main stress indicatorsIII.4-a. Physiological indicatorsIII.4-b. Zootechnical indicators

IV. Measures to be taken during stressful periods

IV.1. Stopping wasting and restarting growth : restore apetite

IV.2. Preventing cardiac and hepatic lesions

IV.3. Eliminating excess free fatty acidsIV.4. Supporting the kidney functionIV.5. Improving immune defenses

and preventing the risk of infectionIV.5-a. Vitamin supplementationsIV.5-b. Antimicrobial treatments

3

Avariety of stressors exist in the rearing of broilers andlaying hens such as handling, transport, crowding and

immune challenge. These stressor factors last from a fewhours to several days or weeks.

Stress control is simultaneously integrated by the neural andendocrine systems. This induces important changes in behavior,physiological parameters, especially hematological, enzymaticand hormonal. The stimulation of adrenal glands has a strongimpact on the liver, heart, kidneys and muscles.

The changes listed above should be taken into account as theywill be quantifiable parameters to measure the degree ofstress, to predict the impact on zootechnical performance andto help implement treatments.

The first measure will be to eliminate the stress factors, as faras possible, and the second to rapidly distribute, dietary sup-plements into the drinking water, in order to restore appetite,support the heart, liver and kidney functions and improveimmune defenses and prevent the risk of infection.

4

I. StressI.1. Definition

Stress is "the result of excessive demands on the physiologicaland behavioural capacities of the bird to adapt’’ (Dantzer).

Each bird is adapted to a given life environment (temperature,feed, housing, physiological status...) within which the organismcan fully express its genetic potential : this is the comfort zone.

Sudden changes in one or several parameters of this environ-ment cause the bird to exhibit an adaptation reaction calledstress. These environmental changes bring the bird out of thecomfort zone, then it can no longer compensate for thesechanges and enters a stress period.

I.2. What are the stress inducing factors ?

The bird's comfort zone is defined by a state of equilibrium ofsix factors: breeder, feeding, building, bird, microbism andflock management (see Figure 1). This equilibrium continuously evolves all along the bird's life (feeding and phy-siological stage for example). Only a sudden change in one ofthese factors results in an imbalance: a stress.

Breeder:- Know-how (during handling,

e. g. vaccination),- Sense of observation.

Feed:- Amino acid, energy, vitamin,

mineral deficiencies,...- Imbalances (Ca/P, lipids...),- Insufficient watering.

Building: - Sudden temperature

changes (day/night,...),- Excessive population density,- Insufficient ventilation

(accumulation of noxious gases : ammonia, carbon dioxide...),

- Equipment.Bird:

- Various physiological changes:- Hatching,- Starter,- Puberty (laying maturity),- Moulting...

Flock management:

- All in-all out flock breeding,

- Elaboration of the group pecking order (competition at feeding trough, fights...),

- Light program,- Type of containment,- Litter.

Microbism:- Hygiene (cleaning,

disinfection, ventilation space ...),

- Sanitary status: pathology or healthy carriage resulting in immunodepression or paving the way for other bacteria (Gumboro, Mycoplasma, Colibacillus...),

- Parasitism,- Handling: injections, debeaking (wounds...),

loading, de-packing, relocation,...- Live vaccines,- Debeaking,- Nervosity,

Fig. 1 - The six factors of equilibriumThe various factors inducing a stress reaction can be grouped under the generic name of aggression factors:

Comfortzone

All these factors have very few consequences when they are indi-vidually active. However, this is seldom the case. Indeed, they aremost of the time combined. Throughout the bird's life, there arecritical phases liable to result in significant stress situations.

This rapidly results in the appearance of pathologies and/or stron-gly impairs the technical and economic performance of the flock.

The following tables give examples of possible stresses inbroilers and layers.

II.1. Chronology of possible stresses for broilers

For broilers, hatching, the starter periodand growth are the critical phases (seeFigure 2). The starter period is a difficultphysiological stage for the chick (imma-turity of its major functions), birds withdifferent immune statuses are mixed,

there is competition at the feeding trough(liable to result in feed deficiencies in the

weakest birds), increased microbism (due to theconcentration of birds), sometimes combined with incompletecleaning-disinfecting-ventilation space of the premises.

II.2. Chronology of possible stresses for laying hens

Similar stresses are observed in layers during the first sta-ges. Then, layers entered a very critical period from the startof laying until the peak of lay which will impact the overalllaying performance (see Figure 3).

5

II. Chronology of possible stresses

Fig. 2 - Critical periods for broilers

Hatching

Starter

Growth

- Fatigue of the chick- Microbism (ambient or latent carriage)

immaturity of the main physiological functions

- Immature physiology transport- Microbism (miscellaneous origins)

breeding conditions (temperature, watering)

- Handling- Vaccination with a live vaccine

- Increase in density- Microbism temperature, ventilation- Feed transitions - Vaccination with a live vaccine

Critical periods Stress-promoting factors

Fig. 3 - Chronology of possible stresses for laying hens

Hatching

Starter

Growth

Laying maturity

Laying period

Moulting

- Fatigue of the chick- Microbism (ambient or latent carriage)

immaturity of the main physiological functions

- Immature physiology transport- Microbism (miscellaneous origins)

breeding conditions (temperature, watering)

- Handling- Vaccination with a live vaccine

- Increase in density- Pecking order microbism- Temperature, ventilation handling

(vaccinations and other injections)- Vaccination with a live vaccine

- Physiological disturbances- Psychological disturbances

(lighting program, change of building, of feeding...)

- Flock management (containment mode...)

- Vaccinations- Density of population

- Physiological disturbances

Critical periods Stress-promoting factors

6

III.1. Alarm phase

The bird that undergoes a shock reacts through the periphe-ral (orthosympathetic) nervous system. It is then in a wake-fulness state.This reaction is reinforced by the secretion of adrenaline (thehormone of the adrenal gland) the effect of which consists inincreasing the general metabolism.

This effect results in:- Increased cardiac rate (tachycardia),- Lung hyperventilation (tachypnea),- Dilatation of the pupilla (mydriasis),- Dishevelled feathers (piloerection),- Increased consumption of dietary energy

(carbonhydrates, lipids)

In the wild state, this results in the bird fleeing away, whichcannot happen in intensive breeding.

III.2. Resistance phase: the bird tries to adapt to its new living conditions

For that purpose, it mobilizes numerous hormones:The ACTH which produces: • Hypocholesterolemia and increased lipid accumulation in the liver,• Atrophy of the lymphoid organs such as the thymus andFabricius' bursa which play a part in the defense of the organism,• Release of cortisol causing (see Figure 5):

- muscle wastage due to protein catabolism,- retarded development of heart that can aggravate

hypoxaemia and ascites,- hyperglycemia due to glycogenolysis/gluconeogenesis,- enhanced secretion of insulin leading to a redistribution

of energy towards fat abdominal deposit,- hyperuricemia,- suppressed immune / inflammatory responses resulting

in immunodepression

III. Physiological mechanism of stressThe adaptation reaction of the organism to an aggression can be divided into 3 phases (see Figure 4):

Fig. 4 - Physiopathology of stress (Ruckebusche, 1981, Selye, 1985)

Stress phase Organ involved Consequences Clinical

Alarm phase

Resistance phase

Decompensationphase

Recovery phase

- Orthosympathetic nervous system

- Hormone: adrenaline

- Hormone: aldosterone

- Hormone : ACTH

- Hormone: Cortisol

- Exhaustion of the organism

- Recovery of the organism

- Wakefulness state

- Tachycardia, Tachypnea,Mydriasis Piloerection

- Mobilization of Glucose and free fatty acids

- Sodium retention- Potassium excretion

- Hypocholesterolemia- Lymphoid atrophy- Lymphopenia

- Immunodepression

- Death

- Gradual clinical recovery

- Nervosity - Breathlessness- Dishevelled

feathers

- Dishevelled feathers - Wet litter

- Symptom(s) of the accompanying pathology(ies)

- Mortality

- Delayed growth

A

G

G

R

E

S

S

I

O

N

7

The defense/aggressor equilibrium is then broken in favour ofthe bacteria. This imbalance will occur all the more easily asthe global metabolism of the organism is weakened (exhaus-tion of energy reserves...).

Aldosterone, increased during this period, also results in uri-nary discharge of potassium and sodium retention, 2 signifi-cant elements in cell metabolism. This phase is more or lessprolonged according to the aggression intensity.

III.3. Decompensation phase

If aggression persists, it leads to the exhaustion of the organism: • mobilization, use and exhaustion of energy reserves,• fatigue of the various vital organs such as the heart

and kidneys,• wear of the main functions such as immune defenses.

The bird is thus weakened and extremely sensitive to the patholo-gical and/or opportunistic bacteria present in its environment. (Figure 6). This results in the bird's death (exhaus-tion and/or pathology) or the economic non-value of its production.If the aggression stops before or at the very beginning of thisphase, the bird may entirely recover and be cured, but itsgrowth will be delayed.

18

16

14

12

10

8

6

4

2

021

Breast weight (%) CORTBreast weight (%) Control

28 35 42

-16%

Age (days)

%

-28%

Fig. 5.a - Effect of cortisol on breast development from 28 d to slaughter age (Lin, 2006)

3

2,5

2

1,5

1

0,5

021

Abdominal fat (%) CORTAbdominal fat (%) Control

28 35 42

+50%

+46%

%

Age (days)

Fig. 5.b - Effect of cortisol on abdominal fat deposit from 28 d to slaughter age (Lin, 2006)

6

5

4

3

2

1

0

Control ACTH Cold stress Corticosterone

Viable count ofE. coli in spleen :Log 10 (CFU/g)

d

a

b

c

Fig. 6 - Suppressive effect of ACTH, cortisol or cold stress treatment on the non-specific immunity against E. coli infection

O1:K1 (p<0,05) (Matsumoto, 2000).

a-d Means within column with different superscript differ significantly (p<0,05)

8

III.4. The main stress indicators

There are not one but many indicators of stress. When ana-lyzing stress, the choice of the indicator depends on the para-meter being affected (well-being, profitability). Usually, the consequences of the stress on health and pro-ductivity are studied, since deleterious repercussions on pro-fitability are certain.

III.4.a Physiological indicators

The main harmful consequences of stress are associatedwith the undesirable physiological effects of glucocorticoidsand catecholamines:

• Reduced appetite following the bird's adaptation to thecause of the stress,• Reduced ability to digest; nutrients are not properly extrac-ted from the feed, due to reduced digestive secretion causingindigestion, increased feed conversion efficiencies,...• Wasting due to hormonally-induced proteolysis, • Excess of free fatty acids due to hormonally-induced lipoly-sis and worsened by a carnitine deficiency,• Reduction in the bird's defense mechanism due to depres-sion of the lymphoid tissue. The ratio heterophil/lympocytes(H/L) which is a valuable indicator is significantly increaseddue to both significant heterophilia and lymphopenia. The birdis less able to resist infections and parasites, leading to poorhealth and high mortality (see Figure 7).

III.4.b Zootechnical indicators

In the breeding, the stress reaction produces a decrease inzootechnical results (see Figure 8).- Retarded growth,- Increase in feed conversion,- Drop in laying,- Decreased egg quality,- Increased mortality,- Depreciation of carcasses,- Multiple-factor pathologies.

The economical consequences are then serious.

69

68

67

66

65

64

63

62

61

60

Low density > 20 birds/m2

+7%%

Fig. 7 - Influence of bird density on the H/L ratio % (p<0,05) (Campo, 2005)

100

90

80

70

60

50

40

30

20

10

0

14

StressControl

28

-42%

g/d

-57%

Age (days)

Fig. 8.a - Influence of chronic stress at 14 and 28 days of age on body weight gain (p< 0,0001) (Lin, 2004))

0,9

0,8

0,7

0,6

0,5

0,4

0,3

0,2

0,1

0

14

StressControl

28

-45%-40%

g/g

Age (days)

Fig. 8.b - Influence of chronic stress at 14 and 28 days of age on feed intake (p< 0,05) (Lin, 2004))

IV. Measures to be taken during stressful periods

Some stresses are directly related to the breeding conditionsand so well known. Suitable prevention measures could beimplemented in order to help the birds manage at best thosestresses (starter period, start of laying, pathologies, feedtransitions, transport, …).

On the other hand, when the stress situation will be installed,the objective will be to help the bird to recover as soon aspossible its confort zone in order minimize the impact on theperformances.

IV.1. Stopping wasting and restarting growth: restore appetite

Under the effect of the stress, and more precisely due to theeffect of the hormones released into the blood stream,

energy production increasesdue to the catabolism oflipids and proteins. This causes the break-down of muscle tissueby proteolysis andthus wasting.The production ofenergy has to be re-establish by thecatabolism of lipids tocounter wasting , sothe amino acids areused instead for growth.

The first need for the bird isto restore its appetite. The birdneeds to resume eating the normalquantities required for its needs as quickly aspossible.

10

The digestive functions should also be stimulated, particularlyby increasing the digestive secretions depressed by stress.Then the full benefit of the feed can be absorbed by re-esta-blishing normal digestion.

IV.2. Preventing cardiac and hepatic lesions

A consequence of stress is an excess of fatty acids due tointense lipolysis.Excess free fatty acids consume carnitine.

Carnitine is a necessary element in the production of energyfrom fatty acids: it acts as a transporter, and is essential inallowing fatty acids to cross into the mitochondria, wherethey can then be catabolized by β oxidation.

Carnitine is biosynthezised in the liver and kidneys.The amount synthezised is sufficient to provide an adult'sminimum requirements under normal conditions, i.e. in theabsence of stress: carnitine is not considered as being anessential nutriment.

When the free fatty acid/carnitine ratio is correct, beta-oxi-dation within the mitochondria is optimal and the storage offatty acids functions optimally and toxic metabolites do notbuild up.

An excess in free fatty acids causes an imbalance, with a defi-ciency in carnitine and leads to fat overload.

This excess quantities of grease in the cell causes celldamage that mainly occurs in the cells of the liver and heart.

Giving rapidly the required carnitine:• Orients the energy-producing catabolism towardthe catabolism of fatty acids pathway, and not via the cata-bolism of proteins,• Allows a more rapid elimination of the excess free fattyacids acting as a detoxifying role.

IV.3. Eliminating excess free fatty acids

Both in relation to catabolism and the elimination of excessfree fatty acids, the body's emunctories, the liver and kidneys,are required to work hard.

Supplements providing B vitamins (particularly biotin) andvitamin E / selenium, sorbitol, magnesium sulphate, vegeta-ble extracts acts in synergy with carnitine to stimulate thehepatic function, intestinal transit, pancreatic secretions anddiuresis.

These ingredients complement perfectly carnitine's role, byeliminating waste products and by stimulating the organism.

IV.4. Supporting the kidney function

Supporting the kidney function will promote elimination ofstress metabolites and excess potassium.

Betaine is one of the main osmolytes present in the avian kidney.

Dietary supplements with betaine-based formulations asso-ciated with mild diuretics will be so recommended.

11

IV.5. Improving immune defenses and preventing the risk of infection

In case of a stress reaction, the organism produces somesubstances (ACTH, cortisol) which induce as a side effect aweakening of the defense system, the defense/aggressorequilibrium is then broken in favour of the bacteria.

The pathological risks related to astress factor are always very

significant. Among the pathologies thatappear with stress, respiratorypathologies (CRD, Coryza, sinu-sitis...) can be mentioned, but

other organs may also be affected(e. g. joints).

IV.5.a Vitamin supplementations

As previously mentioned, the stress reaction strongly dis-turbs the bird's metabolism, leading to an increase in energyconsumption. Now, this energy production consumes vita-mins.Vitamins are substances which the bird cannot produceby itself.Vitamins A, B2, B6 and B12 are known to have an essentialrole in maintaining the integrity of the organism at theimmune system level.

IV.5.b Antimicrobial treatments

Antimicrobial treatments will be implemented as required.Regarding the bacteria, the most adequate molecule will bechosen.

Certain macrolides are known to have a complementaryaction : a direct fight against the bacteria through their antibiotic action and an indirect fight through the stimulationof the immune response. This allows the restoration of theequilibrium disturbed by the stress.

12

14

15

Application of VIGOSINE® in stress

management

I. Action and VIGOSINE®

utilization programI.1. Optimization of fatty acid

catabolism I.2. Prevent of cardiac, hepatic

and kidney damageI.3. Stimulation of feed intake

and digestive secretionsI.4. Practical use of VIGOSINE®

during stressful periods

II. VIGOSINE® trial resultsII.1. Results of VIGOSINE® in pullets

- Protocol- Results- Conclusion

II.2. Results of VIGOSINE® on cardiac mortality in broilers- Protocol- Results- Conclusion

In intensive poultry farming, stress can affect any bird whose

metabolism is adapted to the demanding conditions of this

type of farming: bird handling is frequent, and behavioral pro-

blems caused by confinement and poor environmental quality

are common.

In stressful situations, there is a sudden requirement for

additional energy (for adaptation to stress), however, there is

also a risk of steatosis since the fatty acids mobilized by the

hormonal action (catecholamines, corticosteroids, glucagon)

are not suitable for a correct production of energy.

VIGOSINE® supplied via the drinking water is a convenient way

of assisting birds in meeting their energy requirements rapidly,

and hence to reduce any deleterious effects on zootechnical

performance.

16

I. Action and VIGOSINE®

utilization programThe main harmful consequences of adaptation to stressfulsituation are associated with the undesirable physiologicaleffects of glucocorticoids and catecholamines (Figure 1).

• reduced appetite following the bird's adaptation to thecause of the stress,• reduced ability to digest, nutrients are not properly extrac-ted from the feed, due to reduced digestive secretion causingindigestion, increased feed conversion efficiencies, ...• wasting due to hormonally-induced proteolysis,• an excess of free fatty acids due to hormonally-induced lipo-lysis and worsened by a carnitine deficiency,• a reduction in the bird's defense mechanism due to depressionof the lymphoid tissue. The bird is less able to resist infectionsand parasites, leading to poor health and high mortality.

I.1. Optimization of fatty acid catabolism

Excess free fatty acids, a consequence of stress, consume car-nitine and lead to a secondary deficiency. VIGOSINE® suppliesthe bird rapidly with the required carnitine. It encourages thecatabolism to take the lipid pathway, stops wasting by preven-ting proteolysis, and enables growth to be rapidly resumed inorder to attain correct zootechnical performance.

I.2. Prevent of cardiac, hepatic and kidney damage

Excess free fatty acids cause cell damage due to excess quan-tities of grease in the cell. This damage mainly occurs in thecells of the liver, the kidney and the heart.Weakening of the liver, which is clear in layers and fast-gro-wing chickens, makes it essential to enhance liver function,particularly in chronic stress situations.VIGOSINE® improves elimination of excess fatty acids. In addi-tion, salts and plant extracts have a detoxifying function thatpromotes elimination of metabolic waste products.

I.3. Stimulation of feed intake and digestive secretions

In stressful situations, there is a sudden requirement for addi-tional energy (for adaptation to stress). Paradoxically the stressdepresses the appetite and the digestive secretions. VIGOSINE®

by increasing appetite helps the bird to resume eating the nor-mal quantities required for its needs more rapidly.VIGOSINE® stimulates also the digestive functions: the full benefitof the feed can be absorbed by restoring normal digestion.

I.4. Practical use of VIGOSINE®

during stressful periodsVIGOSINE® is to be used regularly over short periods of time,particularly during difficult periods as far as feeding is concer-ned (starter period, transitions and finisher period for the broi-lers, start of laying and up until the laying peak for the layers).Such use makes it possible to eliminate excess free fatty acidsDistribute the product continuously using a dosing pump, orpour sufficient product directly into the feed tank for half-a-day's consumption.Dosages are expressed as ml of VIGOSINE® per liter of drin-king water.

STRESS

Reduce appetiteand ability to digest

Excess fatty acidsand carnitine

deficiency

Excess of metabolicwaste products

Hepatic overload,cardiac and renal

fatigue

Cell damage causedby excess fatty acids

VIGOSINEEnhances catabolism

of fatty acidsand stops thinning

Facilitates renalexcretion

Supports hepatic,cardiac and kidney

functions

Limits hepatic,cardiac and kidney

damage

Restores appetiteand stimulate digestive

functions

Fig. 1 - Stressful situations: benefits of VIGOSINE®

- Recovering appetite- Utilising fatty acids

(lipolysis)

- Assisting filtering organs

- Preventing the infiltration of grease

1-2 ml / liter for 1 to 3 daysduring and after the stress

Broilers: 1 ml / liter for 2 to 4 days during feed transitionLayers: 1-2 ml / liter for 2days every 3 to 4 weeks untilpeak of lay.

Objective VIGOSINE®

II.1. Results of VIGOSINE®

in pullets

ProtocolA group of intended to be layers were vaccinated (fowl poxand LTI) and debeaked when 10 weeks old. The farm had twobuildings, the birds in one were given aspirin at a dose of0,25g/l for 3 days after the two operations (control popula-tion: 33 462 pullets). The birds in the other house were givenaspirin at the same dose and VIGOSINE® at 2 ml/l for the 4days following two operations (treated population: 20 732pullets).

ResultsImmediately after vaccination and debeaking, a reduction was observed in feed consumption for both groups, followedby a reduction in live weight during the following week. The recovery rates for the two groups were however different(Figure 2).

The control group recovered normal consumption levels 4weeks after the operation; live weight was recovered at amuch larger stage.

The two operations VIGOSINE® group recovered quasi normalconsumption in the week after the operation, and caught upwith the standard growth level after 4 weeks. The averagelive weight for the trial group was greater than the control by2% after 10 weeks, and 12% higher after 16 weeks.

ConclusionThis trial demonstrates that a moderate use of VIGOSINE®

(4 days at 2ml/liter) enables the pullets under vaccination anddebeaking stress to better withstand such stress and recover.

17

II. VIGOSINE®

trial results

Average weight of

the laying hens (g)

VIGOSINEControl

Debeaking

Feed in take

(g/hen/day)

Debeaking

VIGOSINEControl

Age(weeks)

Age(weeks)

Vaccination

Vaccination

Fig. 2 - Results of VIGOSINE® on consumption and weight of pullets after debeaking and vaccination

II.2. Results of VIGOSINE®

on cardiac mortality in broilers

ProtocolThis trial assessed VIGOSINE® against a PLACEBO, each pro-duct being used in a static-ventilation building housing26,400 broilers (initial density: 22 broilers/m2).As soon as the daily percentage of cardiac mortality of 0.1%(verified by autopsy) of the population in either of the buil-dings was reached, the products were randomly assigned tothe buildings and were given at the same time in each res-pective building for 7 days at 2 ml/liter drinking water.Cardiac and overall mortality was then recorded each mor-ning at a set time, as well as performance for each period(growth, feed conversion).

ResultsCardiac mortality reached 0.13% at 16 days in one of thebuildings (B1), while it was 0.10% in the other (B2).Products were added to the drinking water between 16 and23 days of age.In both groups, cardiac mortality increased: +0.5% in theVIGOSINE® group (B1) versus +0.8% in the PLACEBO group(B2) (Figure 3).

While the VIGOSINE® group had a lower weight prior to sup-plementation (-5.5% at D16), its showed a significantlyhigher live body weight at the end of supplementation (+7.1%at D23), and this difference was still partly found at slaugh-ter (+4.1% at D35) (Figure 4).

ConclusionWhile the sudden death rate naturally increased over periodD16-D35, VIGOSINE® made it possible to reduce these los-ses although the group was heavier than the control group atthe end of the rearing period. These results show that VIGO-SINE® reduces the risk for cardiac mortality while optimizinggrowth.The effect on the MDG was observed during the period whenVIGOSINE® was given; these results suggest that it is prefe-rable to use VIGOSINE® over short periods of time (1 day at1 ml/liter), on a frequent basis (once to twice a week), ratherthan using it continuously.

18

0.80

0.70

0.60

0.50

0.40

D1 - D15 D16 - D23 D23 - D35

VIGOSINEPlacebo

Fig. 3 - Effects of VIGOSINE® on cardiac mortality

1.6

1.4

1.2

1

0.8

0.6

0.4

0.2

0

D16 D23 D35

VIGOSINEPlacebo

Fig. 4 - Effects of VIGOSINE® on growth

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