Controversies in the Surgical Management of Sigmoid Diverticulitis

The timing and appropriateness of surgical treatment of sigmoid diverticular disease remain a topic of controversy. We have reviewed the current literature on this topic, focusing on issues related to the indications and types of surgery. Current evidence would suggest that elective surgery for diverticulitis can be avoided in patients with uncomplicated disease, regardless of the number of recurrent episodes. Furthermore, the need for elective surgey should not be influenced by the age of the patient. Operation should be undertaken in patients with severe attacks, as determined by their clinical and radiological evaluation.
Magnitude of the Problem
Diverticular disease, either diverticulosis or diverticulitis, was regarded as a surgical curiosity in the 19th surgery, but over the past 100 years, its prevalence in Western countries has increased dramatically. In the US, an individual’s risk for developing diverticular disease approaches 50% by age 60.1 Diverticulitis, defined as inflammation and infection related to diverticula, occurs in 20 to 30% of patients with diverticulosis and is one of the most common indications for gastrointestinal tract-related hospitalizations. One in four of these patients presenting with diverticulitis will require an emergency operation because of perforation, peritonitis, or systemic complications. At present, diverticulitis is the associated diagnosis for one third of all colostomies and/or colon resections.2 As such, diverticulitis is one of the five most costly gastrointestinal disorders affecting the US population.3
Etiology
Colonic diverticula tend to develop in the areas of weakness in the colonic wall, most frequently at the sites of penetration of the wall by blood vessels.4 These outpouchings of mucosa and peritoneum are of the pulsion type and are thought to be caused by an increase in the intraluminal pressure within the colonic wall in affected individuals (Fig. 1).
Figure 1Endoscopic images of diverticuli. Colonoscopy can be rather difficult when several diverticula are encountered because of increased colonic tortuosity and lack of distensibility.
It is thought that a low intake of dietary fiber and resultant decrease in stool bulk predisposes those in Western societies to an elevation in colonic pressure. Some authors attribute the high rate of diverticular disease to the development of the roller mills during the last half of the 19th century, causing the grains to be crushed so effectively as to nearly eliminate all of the cellulose from the Western diet.5 Despite significant supporting evidence for fiber and its role in the development of diverticulosis, no study to date has demonstrated that a high fiber diet can reverse this process or reduce the incidence of complications in cases of established diverticulosis.6
In addition to dietary intake, other factors have been implicated in the development of diverticular disease. Most studies report that diverticular disease is more common in the elderly, especially elderly women, and in patients who smoke cigarettes or drink alcohol.7 Sigmoid colon specimens from patients with diverticulosis have been found to have increased in vitro sensitivity to acetylcholine, as well as reduced smooth muscle choline acetyltransferase activity and upregulation of smooth muscle muscarinic M3 receptors.8 The significance of these biochemical characteristics still needs to be elucidated, but the differences suggest that there are underlying physiological abnormalities that may predispose to the development and progression of diverticular disease.
Clinical Presentation and Evaluation
The clinical presentations of diverticular disease range from asymptomatic diverticulosis, diverticulosis with periodic spasmodic abdominal pain and bloating, diverticulosis with hemorrhage, and finally, diverticulitis. Although diverticula can occur in any portion of the colon, this review will only focus on sigmoid diverticulitis, by far, the most common site for this disease process.
Most patients with diverticulitis present with symptoms of left lower quadrant abdominal pain, fever, and leukocytosis (Table 1). Additional symptoms of acute sigmoid diverticulitis may include nausea, vomiting, change in bowel habits, urinary frequency, and/or dysuria.1 In cases of clear-cut diverticulitis based upon the clinical picture, one can manage the patient without any imaging studies. In many cases, especially in those with severe symptoms and potential complicated diverticulitis, computed tomography (CT) scanning should probably be performed. The value of CT scanning is the ability to confirm the diagnosis and confidently stratify the severity of the disease process, differentiating mild, localized inflammation from advanced inflammation with abscess formation and/or distant extension.
Table 1Clinical Symptoms of DiverticulitisSymptomsFrequency (%)Left lower quadrant pain93–100Leucocytosis69–83Fever57–100Nausea10–30Vomiting15–25Constipation10–30Diarrhea5–15Dysuria5–20Urinary frequency6–25
Before the advent of CT, the contrast enema was the primary tool in the evaluation of colonic diverticular disease. However, CT scans have largely replaced barium enema as the preferred imaging modality to evaluate patients with suspected diverticulitis. The use of CT scanning has been justified by several studies from the radiological literature, demonstrating a high sensitivity (97%) and specificity (100%) for diverticulitis (Fig. 2). Contrast enema, on the other hand, has a sensitivity of only 82% and a specificity of 81% for diverticulitis.9Figure 2a Computed tomography scan images of a patient who presented with uncomplicated diverticulitis that was subsequently treated successfully with antibiotics. Note the thickening of the sigmoid colon, yet the lack of any extraluminal fluid or air. b Computed tomography scan images of a patient who presented with complicated diverticulitis and an extraluminal fluid collection that did not resolve with attempted CT-guided drainage an required an eventual sigmoid colectomy.
Classification
There are two commonly utilized classifications of diverticulitis. The European Association for Endoscopic Surgeons developed a classification scheme based upon the severity of its clinical presentation.10 In this system, diverticulitis is divided into symptomatic uncomplicated disease, recurrent symptomatic disease, and complicated disease (Table 2).
Table 2Clinical Classification of Diverticulitis (Adapted from Kohler et al. 10)GradeClinical DescriptionSymptomsISymptomatic uncomplicated diseaseFever, crampy abdominal pain, CT evidence of diverticulitisIIRecurrent symptomatic diseaseRecurrence of aboveIIIComplicated diseaseHemorrhageAbscessPhlegmonPerforationPurulent and fecal peritonitisStrictureFistulaObstruction
Another classification system was developed by Hinchey et al.11 and is used to describe the stages of complicated diverticulitis (Table 3). This scheme allows for good communication among surgeons when it comes to describing the various degrees of diverticular perforation, ranging from a localized perforation with a small abscess to generalized fecal peritonitis. Clearly, the proper surgical approach will vary depending upon the Hinchey stage.
Table 3Hinchey Classification of Complicated Diverticulitis (Adapted from Hinchey et al.11)StageDescriptionIPericolic or mesenteric abscessIIWalled off pelvic abscessIIIGeneralized purulent peritonitisIVGeneralized fecal peritonitis
We will refer to both of these classifications when discussing the appropriate management of this disease. Yet another classification, developed by Ambrosetti et al.12, is based upon the CT findings. The criteria of Ambrosetti et al. are being increasingly utilized to stratify patients into optimal pathways for management (Table 4). Thus, patients with mild disease are likely to be successfully managed with intravenous antibiotics, whereas percutaneous drainage and surgery is generally indicated for cases of complicated diverticulitis.
Table 4Ambrosetti’s CT Staging of Diverticulitis (Adapted from Ambrosetti et al.12)Mild DiverticulitisSevere DiverticulitisLocalized sigmoid wall thickening (<5 mm)AbscessInflammation of pericolic fatExtraluminal airExtraluminal contrast
Management of Complicated Diverticulitis
Surgical intervention is rarely indicated in cases of acute diverticulitis because most of these cases will resolve with appropriate antibiotic management. Operations are reserved for cases of complicated diverticulitis, i.e., patients with perforation and peritonitis, abscess formation, fistula, or obstruction. Although this may seem clear-cut, decisions regarding if and when to operate patients with diverticulitis remain a topic of significant debate.
Operation is clearly indicated when the patient presents with perforation and diffuse peritonitis, whether it is purulent or feculent (Hinchey stages III and IV). However, the ideal surgical procedure in such cases of perforation remains a matter of debate. The possible operations advocated range from a simple washout of the abdomen with drainage, as described in a few case reports from Scotland and France, to primary resection with a Hartmann pouch, primary resection with anastomosis, diverting ileostomy, and finally, a primary resection with anastomosis and no temporary stoma. Of these,1,13,14 American surgeons are most likely to perform the Hartmann procedure, which has been advocated as the standard of care for perforated diverticulitis.1 The Hartmann’s resection has proven to be a safe and effective approach, and is based upon the idea that an anastomosis in the setting of acute infection/inflammation is dangerous and associated with a high rate of suture line breakdown.
A simple washout without resection would not be considered an appropriate approach because ongoing infection/inflammation of the involved bowel is likely to occur. There is a paucity of data to support a minimalist, simple washout approach; there are only 18 case reports in the literature describing the technique and its results.13,14 On the other hand, the practice of routine stomas in operations for acute diverticulitis may not be justified. Belmonte et al.15 looked at 277 consecutive patients treated for acute diverticular disease at the University of Minnesota, both urgently and electively. Of these, 88% had a primary anastomosis, most of them without diversion. They found that primary anastomosis was quite safe, with an overall 4% leak rate. Interestingly, none of these leaks were in their subset of patients with Hinchey stage IV diverticulitis, a group that comprised 9% of their total study population.
A systematic literature review of 50 studies comparing a Hartmann’s procedure to a primary resection with anastomosis for perforated diverticulitis found 569 reported cases of primary anastomoses. The reported mortality and morbidity in the patients with an anastomosis was the same as in the patients who underwent the Hartmann’s procedure.16 These data suggest that in a select group of patients undergoing surgery in the acute stage of diverticulitis, an anastomosis is probably safe, even in the milieu of feculent peritonitis.
These data are intriguing, but must be viewed with caution, especially in the case of a very sick or toxic patient with multiorgan system failure and/or shock. In the absence of randomized controlled studies, we still recommend the Hartmann’s procedure in patients with significant purulent or feculent peritonitis, and those patients with any instability related to the systemic effects of sepsis. However, in a patient who is clinically stable, a primary anastomosis at the first operation can be performed even in the setting of perforation (Fig. 3).
Figure 3Gross specimen of the sigmoid colon that was resected from a patient who presented with freely perforated diverticulitis (Hinchey III). Proximal margin extends to the area where the diverticuli end, and the distal margin is at the rectum.
Mention should be made of the meticulous surgical technique that must be used in this situation. The splenic flexure of the colon may need to be mobilized to ensure a tension-free anastomosis. One should imagine the rectum collapsing back into the pelvis with the patient standing upright when deciding on whether the bowel ends are truly free of tension. The margins of resection must be clearly viable with regard to vascularity. Finally, it may be best to avoid the crossed staple lines inherent to the double-stapled technique. Either a double pursestring technique with a stapled end-to-end anastomosis or a standard handsewn anastomosis are preferred when operating in an inflamed milieu.
Preventive Surgery
The question of when to recommend elective, preventive surgery for patients with diverticulitis remains very controversial. Current American Society of Colon and Rectal Surgeons (ASCRS) guidelines suggest preemptive surgery for any patient who has had two attacks of acute diverticulitis, with the intention of preventing another attack that could present with perforation and would necessitate a stoma.1 This recommendation for surgery after the second episode of diverticulitis is based on the data published in 1969 by Parks17 showing that the mortality rate for each subsequent attack of diverticulitis increases from 4.7% during the first admission to 7.8% during each subsequent admission. Parks is also widely quoted for stating that each subsequent episode of diverticulitis is less likely to respond to medical therapy, with a 70% response after the first episode vs 6% response after the third episode.1 However, there are little data to support this concept of poor response to medical treatment in subsequent attacks of diverticulitis. Furthermore, the advent of CT scanning and better antibiotics has improved nonoperative management of these patients. In a modern series of 673 patients with diverticular disease, only 3% of patients required emergency operations during a follow up of 10 years.18 Another 10-year study of 366 patients showed that recurrence was not associated with an increased rate of either complications or less successful medical management.19
Looking at the issue from another angle, Somasekar et al.20 reviewed 108 patients admitted with complicated diverticulitis. Almost all of them (104) required emergency surgery. Interestingly, only 26% of these patients were previously diagnosed with diverticular disease and only three patients had been admitted in the past with a prior episode of acute diverticulitis. In other words, only 2.7% of patients in this group would have benefited from an elective resection. Complications would still have occurred in 92.6% of patients in whom these attacks happened de novo.
Thus, it appears that elective resection might have little impact on the incidence of patients requiring emergency procedures because most of these occur with the first attack of diverticulitis. Subsequent attacks of diverticulitis in the same patient seem to be akin to their previous ones, suggesting that specific patients are predisposed to a set pattern of diverticulitis, and once settled into this pattern they stay within it. The threat of the colostomy bag to a patient who has been successfully managed medically during two previous attacks may be unwarranted and misleading.
In addition, it is important to recognize that elective surgery for diverticulitis is not without complications. Bookey et al.21 demonstrated that elective diverticular disease resection is associated with higher rates of morbidity and mortality than elective colorectal carcinoma resection, with the mortality rate increasing from 0 to 15% with advancing age. Furthermore, colectomy is not a guaranteed cure for diverticulitis, with recurrence rates varying from 3 to 13%. These rates have improved, however, with the recognition that the chances of recurrence are fourfold higher if a colosigmoid anastomosis is performed, emphasizing the importance of resecting the entire sigmoid colon in an operation for diverticulitis.22
With these conflicting data in mind, we maintain that the patients with uncomplicated diverticulitis can be managed nonoperatively regardless of the number of recurrent episodes. Patients who develop complications, such as fistulas, obstruction, or nonresolving smoldering disease, are best managed with surgical resection. Elective surgery may also be offered to patients who have had two or more episodes of severe diverticulitis, as determined by their clinical presentation and CT grade. In addition, elective surgery may be justified in patients with limited access to medical care or in those who are concerned about the negative impact of repeated illnesses with regard to work productivity and/or psychosocial issues.
In elective or semielective circumstances, both open and laparoscopic sigmoid resection with a primary anastomosis have been considered as acceptable methods of treatment.23 Laparoscopy has been shown to be associated with an approximate 10% rate of conversion to open surgery. Interestingly, no direct relationship has been found between the number of attacks of diverticulitis or the timing after an acute attack with regard to complications or conversion rates with laparoscopic colectomy.24
Diverticulitis in Young Men
Many authors believe that diverticulitis is a more virulent disease in younger patients. As such, it has been argued that all patients younger than 50 should undergo elective colon resection after an initial attack of diverticulitis.1,25 This argument arose from studies in the pre-CT era, which were replete with data, indicating a high risk of surgical intervention in young patients eventually diagnosed with diverticulitis. Subsequent authors have argued that these earlier studies were flawed because of a significant rate of unnecessary laparotomies in the younger patients because of erroneous preoperative diagnoses of appendicitis.26 Vignati et al.27 were among the first to challenge the concept that diverticulitis in the young is a more virulent disease. These authors surveyed 40 patients under the age of 50 that where treated with intravenous antibiotics and bowel rest and found that at a 5- to 9-year follow-up, none of these patients required colostomies. One third of them did undergo surgery, but most of these procedures where either elective or, if urgent, still conducive to a successful primary anastomosis.
Guzzo et al.26 performed a retrospective review of 762 patients with diverticulitis treated at their institution from 1990–2000 and found that 76% of the patients under age 50 improved with antibiotics and did not require surgery during their first attack. These rates did not differ from the rates of surgery in the elderly patients. Of the patients treated nonoperatively, only four patients had a recurrence requiring surgery at a later time and only one needed a colostomy. Thirty-eight additional patients underwent preemptive elective surgery based upon their surgeon’s recommendation. One hundred fifty-five patients, 60% of the entire group, did not require surgery at all.26
A prospective study from Switzerland followed 118 patients who had their first attack of diverticulitis and found that recurrence rates in the younger patients were similar to those seen in the older patients, once stratified by their CT severity.28
Based upon these studies, we believe that young patients should generally be treated using the same criteria as older patients, and that the there is no justification for the routine recommendation for surgery after a single attack of diverticulitis in young patients. Elective preemptive surgery should be reserved for those who had at least two episodes of severe diverticulitis, and this decision should be supported by CT scan documentation of prior complicated disease.
Fistulas
As we succeed with the nonoperative treatment of acute diverticulitis, the incidence of fistulas appears to be increasing, reported to occur in approximately 12% of patients.29 Colovesical fistulas account for two thirds of the cases, followed by colovaginal, colocutaneous, and enterocolic cases.30 These patients can present a significant challenge to the surgeon. Some fistulas will close spontaneously as the inflammatory process resolves. Therefore, a selective approach should be used, in which operation is offered to those patients with persistent symptoms after 5–6 months after an acute attack. The most commonly reported symptoms in this group of patients include abdominal pain (43%), pneumaturia (43%), cystitis (40%), fecaluria (38%), diarrhea (15%), and hematuria (5%).31
In the operating room, the surgeon should expect a significant desmoplastic reaction and a contained abscess cavity in the area of fistulization. It may be prudent to place ureteral stents before the procedure, although most fistulas to the bladder will be at the dome and away from the trigone region, allowing relatively safe access for identification, dissection, and closure. Most of these cases should be amenable to resection with primary anastomosis, avoiding the need for a temporary stoma.32
In expert hands, a colectomy can be accomplished by either an open or laparoscopic approach.33 Some authors suggest that these procedures are best performed by surgeons whose main interest focuses on colon and rectal surgery. A study from McGill University comparing outcomes of surgery for diverticulitis-induced fistulas found that colorectal surgeons performed less diverting Hartmann’s and colostomies (5 vs 27%), and had a lower rate of complications, including wound infections and anastomotic leaks.31 It is not clear, however, whether the data from this small study of 121 patients are applicable to all surgeons in all centers.
Diverticulitis in the Immunocompromised Patient
Diverticulitis in immunocompromised patients can be virulent because there is an increased likelihood of free perforation and fecal peritonitis. In addition, the clinical presentation of these patients often underestimates the severity of their disease.34 Marked differences have also been noted in the response of these patients to medical treatment. In the nonimmunocompromised group one should expect that 75% of patients will respond to antibiotics. In contrast, a very large percentage of immunocompromised patients will fail standard, nonoperative treatment.35 As such, most of these patients require urgent surgical intervention, and this is associated with a significantly higher mortality rate: 39 vs 2% in noncompromised patients.35 Given these data, most authors and the ASCRS recommend elective sigmoid resection after the first episode of diverticulitis in immunocompromised patients.1,34–36
Conclusion
The management of patients with sigmoid diverticulitis is still evolving. We should continue to constantly reassess the surgical dogma regarding the appropriate treatment of this common disease entity. Clearly, a randomized controlled study comparing the Hartmann’s procedure to primary anastomosis in the setting of perforated diverticulitis would be worthwhile. It is becoming increasingly clear that mandatory operations may not be warranted in young patients or those with two episodes of diverticulitis. As in other areas of clinical surgery, we must tailor our treatment to the specific situation for each individual patient.

surgical management
sigmoid diverticulitis
elective surgery
diagnosis


Social Patterning of Screening Uptake and the Impact of Facilitating Informed Choices: Psychological and Ethical Analyses

Screening for unsuspected disease has both possible benefits and harms for those who participate. Historically the benefits of participation have been emphasized to maximize uptake reflecting a public health approach to policy; currently policy is moving towards an informed choice approach involving giving information about both benefits and harms of participation. However, no research has been conducted to evaluate the impact on health of an informed choice policy. Using psychological models, the first aim of this study was to describe an explanatory framework for variation in screening uptake and to apply this framework to assess the impact of informed choices in screening. The second aim was to evaluate ethically that impact. Data from a general population survey (n = 300) of beliefs and attitudes towards participation in diabetes screening indicated that greater orientation to the present is associated with greater social deprivation and lower expectation of participation in screening. The results inform an explanatory framework of social patterning of screening in which greater orientation to the present focuses attention on the disadvantages of screening, which tend to be immediate, thereby reducing participation. This framework suggests that an informed choice policy, by increasing the salience of possible harms of screening, might reduce uptake of screening more in those who are more deprived and orientated to the present. This possibility gives rise to an apparent dilemma where an ethical decision must be made between greater choice and avoiding health inequality. Philosophical perspectives on choice and inequality are used to point to some of the complexities in assessing whether there really is such a dilemma and if so how it should be resolved. The paper concludes with a discussion of the ethics of paternalism.
Introduction
Approaches to Screening
A major component of current public health strategy is the provision of screening programmes to allow prevention and early treatment of serious disease. A characteristic of screening is that it involves the possibility of immediate harm in return for the possibility of future benefit. For example breast screening with mammography has a number of substantial possible immediate harms [26, 38, 50]. In 2001 five percent of mammography screens in the US gave a false positive result leading to further testing [53]. Even when further tests result in a diagnosis of breast cancer, about 20 percent of the cases identified will be of ductal carcinoma in situ which has an uncertain course without treatment [50]. Many such cancers are not life threatening but, once detected, are usually treated as such [53]. Such treatments are unpleasant and damaging to health and women diagnosed with ductal carcinoma in situ have similar anxiety levels to those with early invasive breast cancer [39]. In contrast, only a small number of people, relative to the total screened, have their lives saved, even over a considerable period of time. Estimates suggest that 2451 women aged between 50 and 59 need to be screened as recommended over a five-year period to save one life [41].
Because only a few cases of disease will be detected within a healthy population, large numbers need to be screened in order to have an impact on overall population health. Thus high uptake of screening has been encouraged by emphasizing the benefits of participation, reflecting a public health approach to screening [27]. Recently, in the UK, there has been a policy change towards promoting informed choices particularly in screening:There is a responsibility to ensure that those who accept an invitation [to screening] do so on the basis of an informed choice, and appreciate that in accepting an invitation or participating in a programme to reduce their risk of a disease there is a risk of an adverse outcome [32].
One of the factors influencing the move to informed choices has been a concern about patient autonomy [16]. The issue of autonomy has become more salient with the rise of ‘patient-centred medicine’ in reaction to concerns with traditional medical practice and its emphasis on the role of the health professional in medical decision-making. [37]
Informed Choice in Screening
Informed choices have been defined as those based on relevant knowledge, consistent with the decision-maker’s values and behaviourally implemented [28]. To make an informed choice participants need information about their personal risks of developing the condition, what having the screening test will be like, accuracy of the test, and what will happen if the screening test is positive [15]. While the place of this information in facilitating informed choices is obvious, the role of values may be less so. People will, however, attach different values to the possible outcomes of screening. For example those who are more and less socially deprived may place a different value on early diagnosis. The consequences of being diagnosed with a serious condition can have very different implications for those who have material resources and those who don’t, even within a universal healthcare system. While those who have a high level of material resources can use those resources to ameliorate the impact of a diagnosis of serious illness, for those who are more socially deprived such a diagnosis may bring the prospect of increasing poverty and uncertainty and they might thus prefer to delay knowledge of an illness for as long as possible [24].
There has been no research to describe or evaluate the impact of an informed choice policy in screening. One possible impact is that it will reduce uptake of the screening programme with a greater reduction in some groups, for example those who are more socially deprived and already have lower participation in screening. Such a decline in the uptake of screening could be evaluated negatively as contributing to a decline in the overall health of the population or positively as reflecting an increase in the autonomy of the individual. This paper seeks to describe and evaluate the possible impact of an informed choice policy in screening.
Explaining Screening Uptake
Uptake of screening is lowest in those who are most socially deprived. This is a consistent finding across different screening programmes and healthcare systems [20, 29, 48]. Lower uptake among the most socially deprived is, at least in part, a consequence of a lack of material resources, such as transport costs to the screening centre. But when the lack of such resources is controlled for in statistical analyses, differences in uptake remain [23]. Psychological characteristics, among other factors, contribute to explaining those differences [48, 52].
One such psychological characteristic might be time orientation. Psychologists suggest that people use information about the timeframe in which an event occurs to process information about the event and to make decisions. However, people’s responses to the specific timeframe in which an event might occur, vary. Individuals have preferences for certain timeframes which influence their information processing and evaluation of actions and the possible outcomes of those actions. These preferences are called time orientation.
While a number of different time orientations have been identified [55], evidence for their existence is strongest for two of these, future and present orientation. Those who have high future orientation think more about the future and have an awareness of the effects of current actions on future outcomes compared to those with lower future orientation [42]. Future orientation is associated with the practice of health-related behaviours, such as physical activity and healthy eating, that might involve immediate cost for possible future gain [22, 25, 34, 42]. Those who have high present orientation think more about immediate outcomes of their behaviour than those who are less present orientated [42]. High present orientation is also associated with a limited sense of control and fatalism about life events [42] and unhealthy behaviours, such as substance abuse, which result in immediate rather than future rewards [18, 42]. Future and present orientation are largely independent, of one another with each being associated with different patterns of thought and behaviour [18, 56].
Because the possible harms of screening are immediate while the possible benefits occur in the future, time orientation may contribute to explaining screening uptake. Increasing information about the possible harms and limited benefits of screening may therefore have a differential impact on those with different time orientations. Given that time orientation and social deprivation are associated [33, 47], this effect may vary by social deprivation.
Aims
The first aim of this study is to describe the possible impact of an informed choice policy on screening uptake by exploring the relationships between social deprivation, present orientation and expectations of participation in screening. The second aim is to evaluate that impact from different ethical perspectives.
Method
Design
A questionnaire-based descriptive survey.
Sample
A total of 300 participants was recruited. The sample was structured to reflect the English population in terms of age and sex with one third of the sample being drawn from each of the North, South and Midlands of England.
Procedure
Home-based interviews were conducted by a research agency. Questionnaires were completed by interviewers on behalf of participants.
Materials
In the first part of the interview information about diabetes screening, based on that used in previous research [34], was presented to participants (Appendix 1), after which the following measures were completed:Expectations of participation in screening. The mean response to three items measuring intention to participate in screening was assessed on five-point response scales [34, 35] giving a measure with good reliability (Cronbach’s alpha: .85).Time orientation. A brief, nine item version of the Stanford Time Perspective Inventory (Crockett et al. in submission). The Stanford Time Perspective Inventory (STPI) has been extensively validated and used in the study of health behaviour [9, 21, 42, 56]. This brief STPI consists of nine items, measured on five-point rating scales, comprising two subscales with adequate reliability: five items measuring future orientation (Cronbach’s alpha: .67) and four items measuring present orientation (Cronbach’s alpha: .62).Social deprivation: A brief three item measure asking participants to indicate:
Possession of educational qualificationsHome ownership (including having a mortgage).
Those who neither owned their homes nor had any educational qualifications were considered to have the greatest social deprivation (scored as 2); those who either owned their homes or had educational qualifications were considered to have intermediate levels of social deprivation (scored as 1); and, those who both owned their homes and had educational qualifications were considered to have the least social deprivation (scored as 0). This measure was derived from our previous research which indicated that individual level measures of social deprivation showed greater associations with psychological characteristics than did neighbourhood measures such as the Indices of Multiple Deprivation (Crockett et al. in preparation).
Analysis
Statistical analyses were conducted using SPSS version 12. Associations between social deprivation, future and present time orientation and expectations of participation in diabetes screening were examined using Spearman’s rank correlations.
Results
The associations between social deprivation, time orientation and expectations of participation in diabetes screening are shown in Table 1.
Table 1Associations between expectations of participation in screening, social deprivation and present orientation (Spearman’s rho correlation)Present orientationFuture orientationExpectations of diabetes screeningSocial deprivationa−.245***.067.218***Present orientation−.301***−.265***Future orientation.054*** P < 0.001amost deprived scored as 0, intermediate group scored as 1, least deprived group scored as 2
Future orientation was not significantly associated with social deprivation (r = −.067, n = 300, P = .247) or with expectations of participation in screening (r = .054, n = 300, P = .349). However present orientation was significantly associated with both social deprivation (r = .245, n = 300, P < 0.001) and expectations of participation in screening (r = −.265, n = 300, P < 0.001).
Because only present orientation showed associations with social deprivation and expectations of participation in screening, further findings are presented for present orientation only. To illustrate the association between social deprivation, uptake of screening and present orientation, two figures were plotted. Figure 1(a) shows the mean expectation of participation in diabetes screening at each level of deprivation. As social deprivation increases, expectations of participation decrease. A one-point difference between those most and those least deprived indicates a substantial effect of social deprivation on expectations of participation in screening. Figure 1(b) shows the mean expectation of participation between those with high and low levels of present orientation, indicating that those with low present orientation express higher expectations of participating in screening. Figure 1(b) does not indicate such large effects as seen in Fig. 1(a) suggesting that other variables must contribute to the impact of social deprivation and expectations of participation in screening.
Fig. 1Expectations of participation in screening and (a) social deprivation, (b) present orientation, High and low present orientation calculated by means of a mean split
Additional analyses using another part of the data set presented here indicate present orientation explains part of the association between social deprivation and uptake (Crockett et al. in submission).
Summary
The results of this study suggest that present orientation is associated with both social deprivation and with uptake of screening, such that present orientation partially accounts for the relationship between greater social deprivation and lower expectations of participation in screening. The results indicate that psychological factors can contribute to an explanatory framework of screening uptake. This framework suggests that there is an association between social deprivation and present orientation and that decisions about uptake of screening are influenced by the time orientation of those who are invited. This framework further suggests that making the more immediate possible harms of screening more salient, as would happen in an informed choice policy, could reduce uptake of screening in those who are more socially deprived. This framework can be used to identify and evaluate the possible impact of an informed choice policy in screening.
Evaluation
The Possible Impact of Informed Choices on Inequality
The study results suggest that the implementation of an informed choice policy, which makes salient the possible immediate harms of participation, might lead to decreases in uptake of screening among those who are more socially deprived. This decrease is unlikely to be matched by a similar decrease among those who are less deprived, not only because they are less present orientated but also because evidence suggests that those who are more educated, and typically less deprived, are more aware of the limited benefits of screening programmes [12].
A differential decline in uptake of screening is an issue of particular concern. Those who are more socially deprived already have poorer health [7, 17] and are more likely to develop diabetes and its complications [3, 8]. A reduction in uptake of screening among those who are most deprived might widen the existing gap in physical health between those who are more and less socially deprived, running counter to UK government policy of reducing such inequalities [10, 11]. If an informed choice policy does reduce the rate of screening of the most deprived, then there appears to be an ethical dilemma. On the one hand, there can be greater choice but at the ethical cost of increased inequality; on the other hand, greater inequality can be avoided, but at the ethical cost of less informed choice. In the rest of this paper, we aim to describe this dilemma more fully and offer some thoughts about how, in the face of it, an informed choice might be evaluated.
We should say at the start that our aims are limited and that we do not try, nor think it possible, to evaluate an informed choice policy fully in the space available. Our discussion is aimed at those who feel an initial ethical pull both toward reducing inequality and toward informed choice. Among those who feel this pull are the UK government, whose policies are explicitly designed to try to achieve both. Thus we do not aim to persuade those libertarians or elitists who oppose taxation-funded screening programs altogether. Nor do we intend the ethical claims we make to be applicable in all times and places.
In aiming our discussion at those who are attracted both to equality and choice, we do not suggest that the nature of these values is at all obvious. Indeed, one of our major points will be that any evaluation of an informed choice depends on further specification of these values. It might well turn out, as these values are specified, that the dilemma between choice and equality is merely apparent and that a decision between them in the context of screening does not have to be made.
After the ethical characterization of the choice and equality dilemma, we critique a public health and paternalistic approach to screening that is sceptical about the value of choice.
Is There a Dilemma?
As mentioned, it appears that there is a dilemma for those who value both choice and equality if an informed choice policy reduces the rate of screening of the most deprived without significantly reducing the rates for everybody else. It appears that the health of the most deprived would decline relative to others and thus inequality of health would increase. Whether there is actually a dilemma depends partly on what happens to screening rates in practice, but it also partly depends on the characterization of the ethical values, as we shall now show.
In the first place, it is not obvious, even if there are differential impacts on screening rates, that choice would produce greater inequality of health. While maximizing informed choices might result in decreased physical health, by promoting personal autonomy they might increase psychological well-being. Personal autonomy has been related to two specific psychological constructs [51]: perceived control, which has been linked to positive outcomes including coping, personal adjustment and success or failure in a variety of areas of life [46]; and self-efficacy, which is the sense of having mastery over the action needed to achieve a particular end [4]. Self-efficacy is associated with a number of health-related behaviours including uptake of screening [13, 14, 19, 25]. Those who are more socially deprived are not only disadvantaged in terms of physical health but commonly also have lower levels of positive psychological characteristics, such as self-efficacy, which contribute to an individual’s overall well-being and are related to the ability to make autonomous choices in a variety of health and life domains [5].
The point here can be made in two different ways. One is to say that health, as a philosophical concept, is about more than narrowly defined physical health and that the psychological benefits of greater choice for the most deprived are gains in health to them. This leaves it moot whether a reduction in their rates of screening is worse for them in terms of their health, and thus moot whether choice increases inequalities in health. A second way, which avoids the complicated conceptual debates about what health is, puts the point as one about the determinants of health. Even on a relatively narrow construal of health as physical health the psychological gains of choice, such as increased sense of control [51], might improve the physical health of the most deprived [1], again leaving it moot whether choice increases inequalities in health.
Even if there is a conflict between choice and equality of health, it does not follow that there is a conflict between choice and the value of equality. Again, whether there is a conflict depends on further specification of the value. There is a large debate in political philosophy called the `equality of what?’ debate [44]. Fundamentally, however health is characterized and however equality is characterized, health would only be one item in the metric of inequality. Suppose that an informed choice policy causes the health of the most deprived to be lower than it would otherwise have been. The policy also causes their choice to go up. Whether the result is to make them worse off than they would otherwise have been is a complicated question that depends on the relative value of health and choice. Possibly the result should be counted as a gain in equality, since it increases the choice of the most deprived, although possibly not. The point here is that, from the viewpoint of equality, concentrating on inequalities in health is concentrating on only part of the picture.
Not only is the evaluation of choice complicated by debates about health and the metric of equality, it is also complicated by debates over how to understand the value of equality. It is possible to give only an incomplete and sketchy account of this here. Consider three views: utilitarianism, prioritarianism, and egalitarianism. Utilitarianism recommends policies that maximize aggregate welfare [45]. It would recommend reducing inequalities of health if this would indeed maximize welfare. Many utilitarians believe that greater equality would maximize welfare [6]. As for the policy of informed choice, utilitarians would recommend it if it led to greater welfare than the alternative and oppose it if it reduced welfare. In the next section, on paternalism, we make some points about the effects of choice on welfare.
Prioritarianism recommends policies that improve the position of the worst off. Prioritarians disagree among themselves about the extent of the priority that should be given to the worst off, for instance whether small gains to the worst off outweigh large gains to everyone else [30, 31]. However prioritarians decide to evaluate gains to the worst off, there is no necessary connection between their view and favouring equality. Improving the position of the worst off might reduce inequalities in health, but it might also increase them [36, 40]. Egalitarians, by contrast, believe that inequality is in itself bad. For them, there is some value in reducing inequality even if it is bad for some and good for no one [49]. This is not to say that egalitarians would, all-things-considered, want greater equality if it produced no gain in anyone’s welfare. Their attitude to inequalities would depend on the other values they hold [36].
In the face of this sketch of various positions, it is clear that evaluating any inequality produced by an informed choice policy requires more detail about those effects. That inequality increases does not on its own justify opposing the policy. Suppose inequality increases because the most deprived stay the same, on whatever is the right metric for measuring people’s positions, but the position of others improves. Utilitarians and prioritarians should endorse the policy. Egalitarians might oppose it but also might not, depending on the other values they hold. Suppose the position of the most deprived goes down and others’ positions improve. Egalitarians and prioritarians would probably oppose it, although that might depend on how much the most deprived lose and how much others gain. Utilitarians will weigh up the gains and losses to see what maximizes welfare.
In this section we have pointed out some of the complexities of evaluating the policy of informed choice even if we assume some initial ethical commitment to both choice and equality. In particular, we have shown that the initial statement of the dilemma between choice and equality is too crude, and that there might be no dilemma in the end. In describing the complexities we do not want to suggest that a rationally defensible overall evaluation is impossible, only that it is perhaps more difficult than one might think. In the next section, we continue the theme of complexity by pointing to the for a brisk paternalistic public health approach that says that if choice reduces health it must be bad.
Informed Choice, Public Health, and Paternalism
If an informed choice policy really does reduce the screening rates of the most deprived—or, indeed, of the general population—then the argument might be made that the policy is ethically wrong because it would increase morbidity and mortality. The argument might be put in terms of public health, that the disease burden of society would increase, or more directly in paternalistic terms, that individuals would be net worse off for having and making the choice not to be screened, and that either way, an informed choice should not be implemented. While we cannot show decisively that this argument is mistaken, this section points to some of the serious difficulties that face it. We should state at the outset that we understand paternalism in the sense commonly used in political philosophy, where an action is paternalistic only if it is both motivated by concern for the target’s interests and in some way bypasses the target’s own decision-making, for instance by coercing the target or failing to disclose relevant information [54].
Firstly, at the population level any loss of life resulting from an informed choice policy has to be set alongside the negative impacts of a public health approach to screening including death as a consequence of that approach. Emphasizing the benefits of screening results in limited understanding of the harms of screening, including the possibility of false negatives and in turn this leads to an overestimation of the reliability of screening results by both the public and health professionals [38]. This may lead to symptoms of disease being ignored following a negative screening result, delaying diagnosis and treatment [2, 38].
Essentially the same points can be made if the argument is put instead in paternalistic terms, that individuals choose against their best interests when they choose against screening. From the point of view of any given individual facing the choice of whether to undergo screening, not being screened carries a certain risk of morbidity and mortality and so does being screened. Given other costs and benefits of screening, it might be quite rationally self-interested for some individuals to decide to undergo screening while others choose against it. It is likely that in many cases those who are more deprived would indeed value increased life expectancy and it would therefore be appropriate to give those from lower socioeconomic groups information about their higher risk of dying from the disease to inform their personal evaluation of the benefits and harms of participation. However, it is also possible that those who are more socially deprived may value increased life expectancy differently to those who are less socially deprived resulting in a preference to delay diagnosis for as long as possible, even if, in the long term this results in a shortened life expectancy [24]. Thus it is much harder than might be thought to show that those who choose against screening must be acting against their better interests.
Moreover, as we pointed out in the previous subsection, the value of autonomous choice can be intertwined with people’s interests in that having choices can have psychological, and health-promoting, benefits given perceived control and self-efficacy have been linked to good health [1, 5]. This is a further reason to doubt that restricting individuals’ informed choice would promote their overall welfare.
The argument from the benefits of screening against informed choice, in either public health or paternalistic forms, arguably also undervalues autonomy. For many political philosophers, and people more generally, being able to make choices for oneself is good in itself. The value of informed choice is not simply in the extent to which is allows us to choose what is really in our interests. In other dimensions of life, such a choice of career or partner, many people want to make their own choices even if they are less good at selecting than some disinterested observer [43]. Perhaps these reasons to value informed choice carry over to the choice of screening even if people do sometimes get it wrong.
A persuasive paternalistic argument must show that, given the possibility of an informed choice, the people would tend to choose against their interests and that this would justify denying them the choice. We have not shown that no such argument could be made, but we have tried to show the severity of the difficulties that face it.
Conclusions
This paper has shown how psychological research can contribute to assessing the possible impact of an informed choice policy on screening uptake. It suggests that an informed choice policy could lead to a decrease in uptake of screening amongst those who are most socially deprived, resulting in decreases in the physical health of this group. From a public health perspective any decrease in physical health is a matter of concern, particularly if that decrease is greater in those who are more socially deprived. From an informed choice perspective such a decrease in uptake could be interpreted as indicating that people are making autonomous choices based not only on good knowledge, but also in line with their own values. Those who are more socially deprived are more present orientated. They therefore value actions that have positive outcomes immediately and thus, once they understand that the benefits of screening are not immediate, may be less likely to participate in the screening programme.
These results have been evaluated from different philosophical perspectives on health inequality and on choice. This evaluation has not attempted to provide a definitive assessment of whether the introduction of an informed choice policy in screening can be justified in the light of the likely impact on physical health inequalities outcomes across the population. Rather, the evaluation has sought to describe the way in which philosophical approaches to choice and to health inequality can be used to inform further discussions about choosing an informed choice approach to screening over a public health approach.

screening
informed choice
public health approach
health inequality
paternalism
autonomy
utilitarianism
prioritarianism
egalitarianism


Costs and benefits of induced resistance in a clonal plant network

Plant defense theory suggests that inducible resistance has evolved to reduce the costs of constitutive defense expression. To assess the functional and potentially adaptive value of induced resistance it is necessary to quantify the costs and benefits associated with this plastic response. The ecological and evolutionary viability of induced defenses ultimately depends on the long-term balance between advantageous and disadvantageous consequences of defense induction. Stoloniferous plants can use their inter-ramet connections to share resources and signals and to systemically activate defense expression after local herbivory. This network-specific early-warning system may confer clonal plants with potentially high benefits. However, systemic defense induction can also be costly if local herbivory is not followed by a subsequent attack on connected ramets. We found significant costs and benefits of systemic induced resistance by comparing growth and performance of induced and control plants of the stoloniferous herb Trifolium repens in the presence and absence of herbivores.
Introduction
Plants can allocate a limited pool of resources to the three main functions of growth, reproduction and defense, suggesting that increased investments in one function may compromise the others. Empirical studies have shown that constitutive defense can be costly (e.g., tannins, Sagers and Coley 1995; glandular trichomes, Elle et al. 1999). Plant defense theory postulates that inducible defense mechanisms have evolved to reduce these costs by optimizing the temporal match between resource investment into defense and herbivory threats (Herms and Mattson 1992; Agrawal et al. 1999). In the last decades numerous studies have attempted to find costs of induced defense (reviewed in Bergelson and Purlington 1996 and Strauss et al. 2002) but evidence for costs of inducible plant defense remains scarce and inconclusive. More recently, empirical evidence has emerged supporting the allocation cost theory with the help of improved experimental designs, genetic engineering, and biochemical methodology (Baldwin 1998; Van Dam and Baldwin 1998, 2001; Heil and Baldwin 2002).
Inducible resistance is a form of phenotypic plasticity as it allows plants to express an adequate phenotype in response to temporally and spatially variable herbivore damage. Herbivore-induced changes in the phenotypes of plants often relate to trait alterations which reduce the palatability and digestibility of consumed tissue by producing toxic metabolites and/or by up-regulating the production of a variety of defensive compounds. The ecological viability of induced resistance as an efficient defense strategy depends on the balance of costs and benefits associated with plastic defense induction. Assessing the benefits of induced defense in conjunction with possible costs is a prerequisite for estimating the advantages and disadvantages of plastic defense induction as a potentially adaptive form of phenotypic plasticity (Dudley and Schmitt 1996; Schmitt et al. 1999) and hence for understanding potential selection pressures leading to the evolution of induced plant defenses (Agrawal 2000).
Costs of defense have been traditionally measured in terms of decreased plant fitness. Allocation costs refer to a direct fitness decrease as a consequence of resource-mediated trade-offs between defense investment and other plant functions. Recent empirical and conceptual work has provided convincing arguments for the notion that defense induction can also affect fitness in an indirect manner, via a multitude of potentially complex ecological interactions (Van Dam and Baldwin 1998, 2001; Heil and Baldwin 2002; Strauss et al. 2002). These costs are commonly referred to as ecological costs.
Allocation theory suggests that costs of plastic defense induction should be more apparent in low-resource environments than under optimal growth conditions (Herms and Mattson 1992; Bergelson 1994; Bergelson and Purlington 1996; but see van Dam and Baldwin 2001) as the diversion of resources to defense can not easily be compensated for by enhanced resource acquisition. In addition, experiments to detect costs of defense conducted under quasi-optimal conditions are unlikely to reflect realistic situations, and therefore, tend to underestimate plasticity costs. To overcome this problem, several studies have used competitive and/or low-resource environments to quantify costs of induced defense (Siemens et al. 2003 and studies quoted therein). Additionally, previous studies have shown that controlling the genetic background of plants can substantially enhance the chances to detect costs, by removing confounding effects due to genetic variation in the induced response (Bergelson and Purlington 1996; Strauss et al. 2002).
Stoloniferous plants consist of multiple, genetically identical individuals (ramets) that are interconnected by aboveground horizontal stems (stolons). Resource transport within clonal plant networks has been extensively described in the literature (Pitelka and Ashmun 1985; Marshall 1990; Alpert 1996; Alpert and Stuefer 1997). Nevertheless, the importance of stolon connections for the transport of defense agents is a novel aspect (Stuefer et al. 2004) that has only recently been demonstrated (Gómez and Stuefer 2006). Ramets of the stoloniferous herb Trifolium repens are able to systemically induce other ramets after local herbivore damage. On the one hand, this form of physiological integration may confer clonal plant networks with considerable benefits by allowing for a fast, specific and efficient early-warning system among interconnected ramets. On the other hand, the potentially large spatial scale of clonal plant networks may also lead to substantial costs if network members become induced without being threatened by herbivores (Gómez and Stuefer 2006). These costs are due to a potential mismatch in the spatio-temporal scale of plastic defense expression and the dynamics and patterns of herbivore attacks.
To assess the potentially adaptive nature of plastic responses, “it is necessary to demonstrate that the phenotype induced in each relevant environment confers higher fitness in that environment relative to alternative phenotypes” (Schmitt et al. 1999). This is analogous to stating that the induced phenotype should incur costs in herbivore-free environments, while defense induction should lead to benefits in herbivore-exposed environments. To quantify costs and benefits we measured traits related to plant fitness and performance of induced and uninduced T. repens plants in the absence and presence of herbivores. Growing induced and uninduced plants in the absence of herbivores allows for a quantification of possible costs of induced resistance, simulating localized damage (e.g., by small herbivores with a low mobility) and the activation of defense in ramets beyond the feeding range of the herbivore. Benefits of induction, however, can only be assessed in the presence of herbivores after an initial attack, thereby simulating a scenario with mobile herbivores showing active foraging behavior beyond the first place of attack.
In this study we tested the following specific hypotheses:
In the absence of herbivores, systemically induced ramets of clonal plants perform worse than uninduced ramets of the same genotype. This is due to costs of defense induction when defense is not needed.
In the presence of herbivores, induced ramets of clonal plants perform better than uninduced plants, due to an enhanced protection through induced defense.
To test these hypotheses we grew induced and uninduced (control) plants of the stoloniferous herb T. repens together to expose them to mutual competitive interactions, resembling sub-optimal growing conditions in a sward. To quantify costs and benefits of induced resistance we grew plants in herbivore-free and herbivore-exposed environments, respectively.
Materials and methods
Study organisms
Five genotypes of the stoloniferous herb T. repens L. were vegetatively propagated in a greenhouse at a mean temperature of 21°C/19°C (day/night), and at a 16 h/8 h (light/dark) photoperiod. The genotypes originated from natural riverine grassland populations situated along the river Waal, The Netherlands. They had been collected 4 years prior to the start of this experiment and were grown under common garden conditions, eliminating possible maternal and environmental carry-over effects.
The beet armyworm (Spodoptera exigua Hübner) used in this study is a generalist caterpillar with a broad host range. The caterpillar colony was maintained at a constant temperature of 24°C and 16 h/8 h (light/dark) photoperiod. The larvae were reared on an artificial diet described in Biere et al. (2004).
Pre-growth of plant material
We started the experiment with 64 cuttings of each of the five genotypes. The cuttings were planted in pairs in plastic trays (16 cm × 12 cm × 5 cm) using sterilized clay grains as a substrate (Seramis; Masterfoods, Germany). Each tray was fertilized weekly with 50 ml full-strength Hoagland solution before the start of the experiment. At the beginning of the experiment, all cuttings consisted of a main stolon with at least eight fully developed ramets. If present, side branches were removed immediately before starting the experiment.
Experimental design
The experimental set-up (Fig. 1) to measure costs and benefits of systemic induced resistance (SIR) consisted of four peripheral trays placed around a central tray, which we will refer to as the “competition tray”. All trays were of similar dimensions (16 cm × 12 cm × 5 cm). Each of the peripheral trays contained two cuttings with at least eight ramets each. The cuttings in two of those trays received a treatment to induce defense during the entire duration of the experiment (for details see below), while the cuttings in the other two trays remained uninduced (control). Trays receiving the same treatment were placed diagonally opposite each other. The competition tray was placed inside a metal frame (20 cm × 15 cm × 20 cm) covered by mosquito netting (mesh gauge 0.2 cm2) with four small openings on both longitudinal sides. The two youngest ramets of each cutting were inserted through the mesh openings and allowed to grow (proliferate and root) in the competition tray for 19 days. We used five T. repens genotypes, each of which was replicated 4 times to measure costs and 4 times to measure benefits of defense induction. All induced and control plants grown together in the same experimental set-up (as described above) belonged to the same genotype. The experimental systems were randomly distributed on greenhouse benches.
Fig. 1Schematic representation of the experimental set-up to measure costs and benefits of systemic induced resistance (SIR) in a clonal plant network. Control (white) and defense-induced (gray) plants grew from four peripheral trays into a common, central competition tray. The circles represent petri dishes used for a continued controlled herbivore attack (defense induction treatment). To measure costs of SIR, plants grew together in the absence of herbivores in the competition tray (upper drawing). To measure benefits, ten caterpillars (wavy black lines) were added to the competition tray (lower drawing). See Materials and methods for more details
Systemic induction of resistance
Systemic induction of resistance was achieved through a controlled herbivore attack. One S.exigua larva was confined with two leaves in one petri dish mounted on the plants (Gómez and Stuefer 2006). The corresponding ramets of uninduced control plants were similarly enclosed in modified petri dishes but without adding any larvae. The controlled herbivore attack was maintained throughout the course of the experiment, starting on the ramet on the eighth position (counting from the tip of the stolon) from each cutting. When the two ramets inside the petri dish had lost at least 50% of leaf tissue, the petri dish was moved forward on the stolon and the adjacent, younger ramet was inserted into the petri dish. Whenever the induction treatment was moved forward on the induced cuttings, a comparable leaf area was removed with scissors from one ramet of each cutting in the control trays. This was done to compensate for the leaf area loss due to caterpillar feeding in the induced plants. Cutting the leaves with scissors does not induce resistance in T. repens (S. Gómez, unpublished data). The induction treatment started 1 day after the cuttings were placed into the competition tray. If the caterpillar inside the petri dish died, it was replaced by a new one to maintain defense induction.
In order to enhance plant interactions, induced and control plants were grown together in the competition tray. Since all plants growing together belonged to the same genotype, induction effects cannot be confounded with genetic differences in plant traits, including competitive ability, between induced and control plants. All measurements described below were performed on ramets growing in the competition trays.
Costs of SIR
Costs of defense induction were measured as a reduction in plant performance. Costs can be measured after initial herbivore damage (and consequent defense induction) in the absence of subsequent herbivore attacks. To quantify costs of defense induction we measured the following traits which are known to be closely related to plant performance and fitness: total biomass production, relative biomass allocation to leaves, petioles, stolons, and roots, number and length of the main and side stolons and number of ramets on the main and side stolons. We also measured the petiole length, petiole dry mass, leaf area, leaf dry mass of the fourth and fifth youngest ramets of each cutting.
Benefits of SIR
To quantify benefits of SIR we exposed the plants in the competition tray to a second, controlled herbivory attack (referred to as “herbivory treatment”). We released five fourth instar caterpillars on day 16 in the competition tray and then added two and three more on day 17 and 18, respectively, to achieve substantial levels of herbivore damage. The plants were harvested 19 days after the start of the experiment. We quantified benefits of induced resistance by scoring herbivory damage in the induced and in the control plants. At the time of harvesting each ramet on the main stolon was classified according to the leaf area consumed. We visually estimated the damage and assigned each ramet a damage category ranging from 0 to 3. The values corresponded to the following amounts of damage: 0 = no damage, 1 = 1–33%, 2 = 33–66% and 3 = 66–100% of leaf area consumed. We also recorded the position of the damaged ramet on the stolon to investigate possible intra-clonal variation in the damage pattern according to ramet age. In addition to the degree of damage, we measured the dry mass of leaves, petioles, stolons and roots in induced and control plants.
Herbivore preference test
One day before releasing the caterpillars (herbivory treatment) we performed two dual choice tests per competition tray to check whether plants assigned to the defense-induction treatment were systemically induced. For each competition tray we cut off two control and two induced ramets of a similar developmental stage (third-youngest fully expanded leaf). Each control ramet was paired with an induced one and placed together on a moist filter paper in a petri dish to perform a dual choice test. A fourth instar S. exigua caterpillar was placed in the middle and allowed to feed until more than 30% of one of the leaves was consumed or for 48 h. By means of visual estimates the leaf with the largest area consumed was recorded for each choice test. In 78% of the cases more of the control leaf was consumed (sign test M = 23, P < 0.0001; n = 77) than the induced one, confirming that plants in the competition trays that had received local herbivore damage (defense induction treatment) were induced before the herbivory treatment started.
Statistical analysis
Central competition trays were considered the units of replication in all statistical analyses. To avoid pseudo-replication and a consequent inflation of df (Hurlbert 1984), all traits measured on plants (cuttings) in the competition trays were pooled per treatment (by averaging the four control cuttings and the four defense-induced cuttings, respectively) prior to data analysis. Consequently, our experiment had 20 replicates for measuring costs and 20 replicates for assessing benefits. Competing plants cannot be considered independent from each other as, by definition, they change each other’s environment, growth and development. To take this dependence into account we used a repeated measures design to analyze differences between competing plants that belonged to different treatment groups. Repeated measures analysis explicitly considers intrinsic relationships between treatment groups (Potvin et al. 1990).
Costs of SIR
Repeated measures ANOVA was performed to test for costs of defense induction in number and length of the main and side stolons and number of ramets on the main and side stolons, relative biomass allocation to roots, stolons, petioles and leaves and petiole length, petiole dry mass, leaf area, leaf dry mass of the fourth and fifth youngest ramets. Defense induction (induced vs. control) was considered a within-subjects effect, and genotype was treated as a between-subjects effect. Absolute dry masses of roots, stolons, petioles and leaves were analyzed using two-way repeated measures ANOVA (within-subjects effect—defense induction; between-subjects effects—plant genotype and herbivory).
Benefits of SIR
The amount of damage in the herbivory treatment was assessed with doubly repeated measures ANOVA using ramet age and defense induction as repeated factors and genotype as main effect. The analysis included a profile analysis (SAS procedure GLM; profile statement) to test for differences in the degree of damage between adjacent ramets on the stolons. To correct for differences in the developmental stage of different cuttings we used only the six youngest ramets of each cutting in the damage analysis. All analyses were conducted with SAS 9.1 (SAS Institute, Cary, N.C.).
Results
Costs of SIR
Total dry mass did not differ between control and induced plants (Table 1). However, defense induction caused a significant reduction in petiole dry mass. Additionally, defense induction resulted in a shift in biomass allocation to the different plant parts. Relative biomass allocation to leaves increased significantly after defense induction (Table 2; P = 0.01). The percentage of biomass allocated to roots, stolons and petioles did not significantly differ between control and induced plants. (Table 3)
Table 1Repeated measures ANOVA for effects of genotype, herbivory and defense induction on roots, stolons, petioles, leaves and total dry massSourcedfRootStolonPetiolesLeavesTotalMSFMSFMSFMSFMSFBetween-subject effectsGenotype (Gen)49817.20***3,7104.12***3,74110.97***11,00210.85***60,3778.99***Herbivory (Herb)128.10.2178.60.091,6464.83*4,2344.18*11,9261.78Gen × Herb449.30.361240.141050.312920.291,1710.17Error301368993421,0146,714Within-subject effectsInduction (Ind)179.80.815741.974165.11*98.60.371,8790.99Ind × Gen453.90.5483.10.2850.70.623671.371,0540.55Ind × Herb11061.0757.10.2011.10.141600.601,1430.60Ind × Gen × Herb41391.405421.861591.952650.993,5251.85Error3099.029281.32681,901*0.01 < P < 0.05, ***P < 0.0001 Table 2Costs of systemic induced resistance (SIR). Repeated measures ANOVA for effects of genotype and defense induction on relative dry mass allocation to roots, stolons, petioles and leaves on plants without an herbivory treatment in the competition traySourcedfRootsStolonsPetiolesLeavesMSFMSFMSFMSFBetween-subjects effectsGenotype (Gen)429.86.61** 49614.57***22.73.54*35.77.3**Error154.51276.44.9Within-subject effectsInduction (Ind)112.02.060.040.015.31.9235.87.32*Ind × Gen42.20.388.21.161.80.6410.92.24Error155.87.12.84.9*0.01 < P < 0.05, **0.001 < P < 0.01, ***P < 0.0001 Table 3Average (±SE) absolute and relative dry mass allocated to roots, stolons, petioles and leaves of uninduced and induced plants in the absence of a subsequent herbivory treatment (Costs) and in the presence of a subsequent herbivory treatment (Benefits) in the competition trayRoot (mg)Stolons (mg)Petioles (mg)Leaves (mg)Total (mg)CostsUninduced15.6 ± 3.0 (4.5 ± 0.7%)103.2 ± 6.7 (34.9 ± 1.0%)72.6 ± 4.8 (24.9 ± 0.6%)107.5 ± 8.3 (35.7 ± 0.7%)298.9 ± 21.1Induced11.3 ± 2.1 (3.4 ± 0.6%)96.1 ± 6.0 (34.8 ± 1.0%)67.3 ± 4.5 (24.2 ± 0.5%)106.8 ± 8.3 (37.6 ± 0.6%)281.6 ± 19.1BenefitsUninduced14.5 ± 2.2 (5.1 ± 0.8%)99.5 ± 4.8 (37.6 ± 0.8%)62.8 ± 3.7 (23.8 ± 0.8%)90.1 ± 5.6 (33.5 ± 0.8%)266.9 ± 13.2Induced14.8 ± 3.7 (4.8 ± 0.9%)95.8 ± 6.1 (36.8 ± 1.1%)59.0 ± 4.5 (22.6 ± 0.6%)95.1 ± 7.6 (35.8 ± 0.6%)264.7 ± 19.7
The number of ramets produced on the main stolon was 7% lower in induced as compared to control plants (Table 4; induction effect P = 0.003). The number and length of side stolons and the number of ramets formed on them did not change after defense induction.
Table 4 Costs of SIR. Repeated measures ANOVA for effects of genotype and defense induction on plant fitness and performance-related traits in the absence of herbivoresSourcedfRamet no. main stolonLength main stolonRamet no. side stolonsLength side stolonsSide stolons numberFourth ramet petiole lengthFourth ramet areaMSFMSFMSFMSFMSFMSFMSFBetween-subjects effectsGenotype (Gen)42.383.41*23.55.4***71.96.72**30.81.6316.012.97***18.014.93***8.5715.36***Error150.694.3110.718.91.231.200.55Within-subject effectsInduction (Ind)11.8012.13**7.572.451.250.250.780.230.150.314.385.22*0.100.23Ind × Gen40.171.193.921.271.830.374.101.220.120.240.350.420.090.21Error150.143.084.953.370.510.840.46*0.01 < P < 0.05, **0.001 < P < 0.01, ***P < 0.0001
The fourth and fifth youngest ramets on the main stolon produced petioles 5% shorter in the induced plants (Table 4; fourth ramet P = 0.03, fifth ramet P = 0.07). Leaf area, leaf dry mass and petiole dry mass measured on those ramets were not significantly affected by the induction treatment.
Benefits of SIR
Defense induction had a very strong effect on the amount of damage inflicted by S. exigua larvae on the plants (Table 5; induction effect P < 0.0001; Fig. 2). The number of ramets that were partially or fully consumed during the herbivore attack was consistently higher in control than in induced plants. Most of the damaged ramets lost only a small part of their leaf area (1–5%). This was consistent for both control and induced plants (Fig. 2). In induced plants up to 44% of the ramets on the main stolon were not damaged, whereas in control plants only 22% of ramets on the main stolon were undamaged.
Table 5Benefits of SIR. Doubly repeated measures ANOVA for effects of genotype, defense induction and ramet age on leaf area loss due to herbivorySourcedfMSFBetween-subjects effectsGenotype (Gen)41,1022.39†Error15461Within-subjects effectsInduction (Ind)16,84763.92***Ind × Gen42442.28Error (induction)15107Age518,988133.0***Age × Gen206304.41***Error (age)75142Ind × Age51251.22Ind × Age × Gen201721.67†Error (Ind × Age)75103† 0.1 > P > 0.05, ***P < 0.0001Fig. 2Average damage (±1 SE) inflicted on ramets of the main stolon (the 1st ramet being the youngest and the 6th being the oldest) of control and induced plants in the competition tray after carrying out a controlled herbivore attack (herbivory treatment). Damage categories: no damage (0), 1–33% (1), 33–66% (2), 66–100% (3). The asterisks above the bars indicate the statistical significance of the result of a profile analysis (SAS procedure GLM; profile statement) to test for differences in the degree of damage between ramets of successive age classes. The amount of damage was significantly higher for control than for induced plants in all age classes. ***P < 0.001, ns not significant
The herbivory treatment significantly reduced the biomass of leaves and petioles (Table 1; P = 0.049 and P = 0.036, respectively; Table 3) in both induced and uninduced plants. In the presence of herbivores, induced and uninduced plants had a comparable total biomass. However, induced plants showed a larger percentage of biomass in their leaves (Table 3; repeated measures ANOVA; F = 17.44 P = 0.0008), suggesting that the induced plants benefitted from increased relative biomass in those organs under attack.
Ramet age, regardless of the induction state, had a very strong effect on herbivore preference (Table 5; age effect P < 0.0001). Younger ramets, especially the first and second youngest ones, were heavily preferred over older ones (profile analysis; Fig. 2). The first ramet exhibited particularly severe damage in both induced and control plants (average leaf area consumed > 65%; Fig. 2).
Defense induction had a significant effect on leaf area loss due to herbivory in all ramet age classes (Fig. 2). The degree to which systemic defense induction reduced herbivory damage was similar for ramets of all age classes (Table 5; no age × induction effect). There was a marginally significant genotype effect on the feeding of the caterpillars (Table 5; genotype effect P = 0.09).
Discussion
Our study provides empirical evidence of significant costs and benefits of SIR in a clonal plant network. In agreement with our hypotheses, induced and control plants showed clear differences in performance and fitness-related traits when grown in the absence and presence of herbivores. In environments without herbivores, induced plants produced fewer ramets, shorter petioles and exhibited a shift in biomass allocation patterns. In environments with herbivores, control plants suffered consistently higher degrees of leaf damage than induced plants. Even though defense induction resulted in changes in plant growth, and significantly affected the amount of damage caused by the herbivores, total plant biomass did not respond as expected under the adaptive plasticity hypothesis (Dudley and Schmitt 1996; Schmitt et al. 1999), as we could not find a significant induction × herbivory interaction effect. However, we propose that the differences observed in our study (e.g., reduced ramet production rates and shorter petioles in the cost experiment, decreased amount of leaf damage in the benefits experiment) are likely to translate into substantial differences in plant productivity, and hence biomass, in the longer term.
Costs of SIR
Biomass production and allocation
Total plant biomass production did not change as a consequence of defense induction, implying that defense induction did not incur direct and immediate productivity costs. After induction, however, biomass allocation shifted significantly towards the leaves. We suggest that this allocation shift may enable plants to better cope with current and future herbivory by reducing resource allocation to those organs that are not currently impacted by herbivore damage. While potentially beneficial in the short term, this response might result in longer term indirect costs due to reduced performance under certain environmental conditions, such as drought, root herbivory and severe root competition. A similar shift in the biomass allocation pattern was observed in Lepidium virginicum plants after defense induction. Induced plants grown at a high density showed a reduction in root biomass and an increase in aboveground biomass (Agrawal 2005). In agreement with our findings, total biomass production was not significantly altered by defense induction in that study. A reduction in belowground biomass was also reported for induced wild parsnip plants. In this case, however, the aboveground biomass did not change significantly after defense induction (Zangerl et al. 1997). Further studies are necessary to assess the generality, functional significance (including costs and benefits) and mechanistic basis of changes in root–shoot allocation in response to induced resistance to herbivory.
Reduction in developmental growth rate
Defense induction negatively affected plant fitness by reducing the number of ramets produced. This delayed developmental growth rate was expressed as a reduction in the number of ramets on the main stolon produced during the experiment (7.4 ramets on the control and 7.0 on the induced plants). In the shorter run (i.e., time span of this experiment) this effect is unlikely to translate into biomass differences. In the longer run, however, subtle changes in the developmental growth rate are known to result in very major divergences in performance, structure and clonal fitness of stoloniferous plants (Birch and Hutchings 1992a; Birch and Hutchings 1992b; Huber and Stuefer 1997; Stuefer and Huber 1998).
Reduction in petiole length
Defense induction had significant negative effects on petiole lengths. This effect can have severe performance and fitness consequences for a stoloniferous plant like T. repens, which often grows in dense herbaceous canopies, and which relies on petiole elongation for shade avoidance (Huber 1997). Petiole length largely determines the ability of stoloniferous plants to place their leaves higher up in the canopy (Huber and Wiggerman 1997; Weijschedé et al. 2006). Even a small reduction in petiole length could have serious performance costs since differences in the relative position of leaves in herbaceous canopies are likely to be amplified by asymmetric competition for light (Weiner 1990; Pierik et al. 2003). Defense induction may also cause physiological trade-offs which impede the simultaneous expression of plasticity to herbivores and to shading by competitors (Cipollini 2004). A decrease in petiole length as a result of defense induction can hence, compromise the competitive ability of plants and result in an enhanced risk of induced plants being over-shaded by neighbors. A recent study by Kurashige and Agrawal (2005) supports this notion by showing that Chenopodium album plants, which had previously been damaged by herbivores, were able to elongate stems to a similar proportional degree as undamaged plants when grown in competition for light. However, the damaged plants were smaller due to the expression of induced resistance, thereby incurring potential opportunity costs due to asymmetric competition.
Benefits of SIR
Reduced damage
Our results provide direct evidence for short-term benefits of having an early-warning system in clonal plant networks. In the presence of herbivores, induced plants suffered considerably less damage than control plants. As many as 50% fewer ramets were attacked in induced plants as compared to controls. Localized damage (defense-induction treatment) resulted in a greater degree of protection against herbivores for ramets further along that main stolon and its side branches. The reduced damage did not translate into a significant effect of defense induction on biomass production, due to the fact that the youngest, usually not fully developed leaves were heavily preferred by the herbivores. The biomass loss due to young leaf consumption is very likely to strongly underestimate the negative effects of herbivory and defense induction on future plant growth and performance. Coleman and Leonard (1995) demonstrated how leaf area consumption, and its consequences for plant performance, can be severely underestimated if the developmental stage of leaves is not taken into account. They showed that a certain amount of damage inflicted on young expanding Nicotiana tabaccum leaves is more detrimental than the same amount received by mature, fully developed leaves. As leaf tissue expanded, the area of the holes increased almost fourfold and the final area of the leaf decreased by approximately 40%. In addition, they observed a 35% decrease in the number and mass of fruits on the plants that received the damage to expanding young tissues. Therefore, an initially small amount of damage inflicted on young developing leaves may have dramatic consequences for plant performance and fitness over time. Similarly, the differences found in our experiment can be expected to result in considerable performance differences between induced and uninduced plants as increased damage and loss of young leaves in uninduced plants will compromise plant productivity by reducing the number of future source ramets.
Our results show that ramet age largely determines herbivore damage. The first and second ramets were heavily attacked as compared to the rest. This damage, although still large, was significantly reduced in induced plants. The reduction in leaf area loss in induced young ramets likely increases their chance of survival and establishment. Young ramets in clonal plants constitute the most valuable tissue since they represent the future reproductive potential of the plant (Huber and During 2000) and their protection is critical since they are responsible for a high proportion of the future biomass production (Beinhart 1963). We present evidence supporting the hypothesis that an early-warning system after herbivory in a clonal plant network grants vulnerable young offspring ramets with parental support (Stuefer et al. 2004) that non-clonal plants are unable to confer their offspring at the moment of the attack (but see Agrawal et al. 1999).
Our study provides evidence for significant costs and benefits of systemic defense induction in T. repens. The experimental approach used in this study, however, does not allow for balancing costs and benefits in terms of plant fitness and overall plant performance, because both positive and negative effects of induction reported here, although likely to have significant longer-term effects on productivity and ultimately on fitness, did not have an effect on biomass at the short time scale during which the experiment took place. While our results indicate clear advantages and disadvantages of network induction in the subsequent presence and absence of herbivores, respectively, an accurate and reliable quantification of the cost–benefit ratio should make use of long-term experiments.
In conclusion, the present study shows that in the short term, the activation of early-warning responses in clonal plant networks has both costs and benefits. In the absence of herbivores, the performance of the induced phenotype was compromised as compared to the uninduced phenotype in terms of potential competitive ability. In the presence of herbivores, the induced phenotype was favored by suffering considerably less herbivore damage suggesting potential advantages for the phenotype correctly matching its environment. Whether this represents an adaptive value of the induced responses remains to be demonstrated in longer-term studies where the initial small changes observed in our study can be measured directly in terms of fitness. The long-term balance of costs and benefits of induced resistance in clonal plant networks is likely to be strongly context dependent and a function of the match between spatio-temporal aspects of systemic defense expression and the feeding behavior of herbivores.

plant defense
trifolium repens
physiological integration
adaptive plasticity hypothesis
plant communication